This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
StatPearls [Internet].
Show detailsContinuing Education Activity
Keratitis is a clinical entity wherein inflammatory cells infiltrate different corneal layers in response to noxious stimuli, either infectious exogenous agents or self-antigens. The inflammatory reaction may result in the suppurative melting of corneal epithelium and stroma, resulting in the formation of ulcers. This results not only in the loss of corneal clarity but also threatens the integrity of the globe. Such cases may result in corneal blindness. This activity helps clinicians identify the etiological agent at the earliest based on clinical features and appropriate diagnostic tests and manage these patients with the latest treatment options. It reviews the role of the interprofessional team.
Objectives:
- Review different types of keratitis
- Outline the appropriate evaluation of keratitis.
- Summarize the management options available for keratitis.
- Describe interprofessional team strategies for improving care coordination and communication to advance the care of keratitis and improve outcomes.
Introduction
Keratitis is the inflammation of the cornea and is characterized by corneal edema, infiltration of inflammatory cells, and ciliary congestion. It is associated with both infectious and noninfectious diseases, which may be systemic or localized to the ocular surface. Amongst the types of keratitis discussed above, "microbial keratitis" accounts for the majority and is primarily a cause of major concern in developing countries. However, noninfectious keratitis can not be looked down upon, especially in developed nations.
Our first line of defense is strong enough to dispel most of the infection, causing insults; however, there exist some organisms that can evade this line and cause infection. The corneal epithelium is one such barrier. Most of the organisms cannot penetrate intact epithelium, so they cannot incite keratitis in the absence of cellular injury. Neisseria meningitides, N. gonorrhea, Corynebacterium diphtheria, Haemophilus influenzae, and Listeria species are virulent organisms with the potential to penetrate even intact epithelium and cause keratitis.[1] This article discusses the etiology and available current and future management options for different types of keratitis.
Etiology
Based on the etiological agent, keratitis can be classified as:
Infectious Keratitis
- Bacterial keratitis - including Pseudomonas, Staphylococcus, Streptococcus, Moraxella, Nocardia, and Atypical Mycobacteria
- Protozoal keratitis - including Acanthamoeba
- Fungal keratitis - This includes infection by Aspergillus, Fusarium, Candida (yeast), Cladosporium, Alternaria, Curvularia, and Microsporidia
- Viral keratitis - This includes infection by Herpes simplex virus (HSV), Herpes zoster virus (HZV), Adenovirus, and others.
- Helminths- Onchocercal keratitis (sclerosing keratitis).
Non-infectious Keratitis
- Local causes - include trichiasis, giant papillae, foreign body in sulcus subtarsalis
- Peripheral ulcerative keratitis
- Collagen vascular diseases, like rheumatoid arthritis, granulomatosis with polyangiitis, polyarteritis nodosa, relapsing polychondritis, systemic lupus erythematosus, and others[4]
- Neurotrophic corneal ulcer (post-herpes zoster ophthalmicus, trigeminal nerve damage due to surgery or tumor)[4]
- Xerophthalmia
Epidemiology
In an epidemiological study in California, the incidence of ulcerative keratitis was found to be 27.6/100000 person-years.[5] Ulcerative keratitis was significantly higher among contact lens wearers.[5]
As per a study conducted in South India, middle-aged males were more likely to get corneal ulcers compared to females.[6] Farmers are at high risk on account of their occupation. Fungal corneal ulcers are very common in developing nations. However, HSV is a major concern in developed nations.[7] In an epidemiological study in Rochester, Minnesota, the incidence of epithelial disease was 15.6/100000 person-years, and for stromal keratitis, it was 2.6/100000 person-years.[8]
Autoimmune disorders related to keratitis account for an estimated incidence of 3 per million per year.[9]
The prevalence of xerophthalmia was almost 21% in a study in rural Ethiopia and was largely associated with other features of generalized malnutrition.[10] For xerophthalmia, the population at risk is largely young children who are malnourished.
Pathophysiology
Stages of Corneal Ulcer
- Stage of progressive infiltration
- Stage of active ulceration
- Stage of regression
- Stage of cicatrization
Infectious Keratitis
Infection incites the recruitment of polymorphonuclear leukocytes and macrophages. The hydrolases and proteases released by these inflammatory cells are primarily responsible for corneal stromal melt and necrosis.[11] In gram-negative infections, endotoxin plays a major role and adds to the inflammatory response.
Adenoviral Keratoconjunctivitis
- Stage 1 lasts 7 to 10 days and is characterized by diffuse punctate epithelial keratitis.
- Stage 2- After 7 days, subepithelial to anterior stromal infiltrates appear. NK cells are the first to come into action and further involve cell-mediated immunity.[12]
- Stage 3- This is characterized by persistent subepithelial to anterior stromal infiltrates.
Onchocerca Volvulus Induced Keratitis
Corneal infection by motile worms does not per se cause blindness; however, as they die after chemotherapy or naturally, they incite inflammation and cause corneal punctate opacification. Repeated episodes result in complete opacification of the cornea and result in blindness.
Peripheral Ulcerative Keratitis
The exact etiology is not clear; however, both cell-mediated and humoral immunity play an important role. In response to a corneal antigen, the immune complex gets deposited in the peripheral cornea. The hypersensitivity reaction to an exogenous antigen is other described mechanisms.[13]
Xerophthalmia
Vitamin A is needed for the maintenance and integrity of the epithelial lining of the ocular surface. The loss of epithelial lining with subsequent liquefactive necrosis of the cornea results in keratomalacia.
Histopathology
Corneal infections often start as epithelial ulceration. This is followed by stromal infiltration by polymorphonuclear (PMN) and lymphomononuclear cells, which in turn causes the destruction of Bowman's layer and then stromal necrosis. In severe cases, there can be perforation of the Descemet's membrane. Suppurative infections lead to infiltrates in the anterior two-thirds of the stroma and abscess formation. Epithelial regeneration, vascularization, edema, giant cell reaction, myofibroblatic transformation and stromal remodeling (scarring), and round cell infiltration can occur with chronic infections.
History and Physical
The most common complaints of patients with keratitis include redness, pain, and irritation in the eye. The patients may also present with photophobia, visual decline, or cosmetic blemish.
Bacterial Keratitis
Keratitis by gram-positive organisms: Staphylococcal keratitis can be either because of direct invasion of the organism or because of staphylococcal antigen. Staphylococcal antigen-induced keratitis usually affects the peripheral cornea, hence the name 'marginal keratitis.' Marginal keratitis is invariably associated with staphylococcal blepharitis. The corneal lesions usually start at 10, 2, 4, and 8 o'clock positions, where the lid margin is in contact with the limbus. There is always a clear area between the limbus and the ulcerative lesion, unlike HSV marginal keratitis.
The most common cause of Streptococcal keratitis is a blocked nasolacrimal duct. So, lacrimal duct patency or regurgitation on pressure over the lacrimal sac (ROPLAS) should be evaluated in corneal ulcer cases.
In early-stages of Gram-positive infection, the cuff of cellular infiltration is noted around the corneal focus of infection and is not diffuse, unlike Pseudomonal keratitis.
Pseudomonas keratitis: In early-stage, diffuse and dense corneal cellularity is noted much beyond the focus of infection. Pseudomonas is a gram-negative bacteria with predominantly greenish-yellow corneal infiltrate and extensive collagenolysis. The symptoms are more acute and rapidly progressive. Corneal melt might progress to corneal perforation or endophthalmitis if not taken care of in the early stages.
Nocardia keratitis: Nocardia is a weakly acid-fast bacteria (Modified Kinyoun stain).[14] There may be a history of either trauma or intraocular surgery with corneal infiltrates usually starting adjacent to the surgical incision site. The infiltrates are granular, superficial to mid-stromal, with a wreath-like pattern often in the mid-peripheral cornea.[15]
Atypical mycobacteria: The Atypical mycobacteria are acid-fast bacilli causing keratitis with a protracted course. There may be a history of trauma with corneal foreign bodies or a history of corneal surgery (LASIK).[16] The onset of keratitis in trauma cases can vary from days to weeks; however, post-LASIK cases usually have an average time of presentation of 3.4 weeks.[17] The disease has a waxing and waning course.[18] The corneal infiltrate has a typical cracked windshield appearance with radiating lines in the middle one-third of the corneal stroma.[19]
Viral Keratitis
Adenoviral keratitis: Adenoviral keratitis often has associated conjunctivitis, so the exact terminology would be Epidemic adenoviral keratoconjunctivitis (Human adenovirus types 8,19,37 and 54). Presentation is usually unilateral; however, it becomes bilateral later. A predominantly follicular reaction is noted.[20] It may or may not be associated with conjunctival hemorrhages.[21] At times, the inflammation can be severe enough, resulting in the formation of pseudomembranes. Clinically, corneal epitheliopathy develops, manifesting as punctate corneal erosions, which over a week develop into multiple punctate to nummular anterior stromal infiltrates.[21][22] Preauricular lymphadenopathy is an important finding in adenoviral keratoconjunctivitis. In the pharyngoconjunctival variant (human adenovirus types 3,4, and 7), the patient may have systemic findings like pharyngitis and fever. The corneal findings in the early stage (subepithelial to anterior stromal infiltrate) are considered to be due to active viral replication; however, in the chronic stage, the infiltrates are the result of an immunological reaction.[21] In the chronic stage, symblepharon can also be seen.[23][24] The patients at this stage often complain of photophobia, glare, and haloes.
Herpes simplex keratitis: HSV keratitis can present as epithelial disease, stromal keratitis, and endotheliitis.[25] HSV epithelial disease manifestation may vary from multiple punctate erosions to dendritic ulcers and geographical ulcers. The early vesicular stage is often missed because of delayed presentation to the ophthalmic clinic. The ruptured vesicles coalesce together to form dendrites with a terminal bulb.[26] Inappropriate and indiscriminate use of topical steroids may result in geographical ulcer formation. In epithelial disease, the virus is actively involved in the causation of the ulcer.[27] HSV epithelial disease is usually unilateral, but the bilateral disease is more commonly seen in immunodeficient and patients with a history of atopy.[28] HSV stromal keratitis can either be secondary to epithelial disease due to contiguous spread or immune-mediated. If stromal keratitis develops secondary to epithelial disease, an overlying epithelial defect is present. However, the primary stromal involvement manifests as localized stromal edema with or without signs of previous similar episodes. On resolution, these result in scar formation. These scars with vascularization are the telltale signs and are also called 'footprint scars' with or without superficial or deep vascularization. HSV endotheliitis manifests as localized or diffuse stromal edema with underlying keratic precipitates.
HSV necrotizing stromal keratitis is a variant where both the viral load and the inflammatory component play roles simultaneously.[29][30] It manifests as corneal stromal infiltrate with extensive collagenolysis and corneal thinning. If not treated early, corneal perforation is likely.[31]
Herpes zoster keratitis: The diagnosis of Herpes zoster ophthalmicus (HZO) is very obvious. Associated unilateral rashes over the forehead and eyelids with rashes reaching the tip of the nose (Hutchinson's sign) suggest likely involvement of the corresponding eye also.[32] Corneal dendritiform lesions with absent terminal bulbs are very characteristic.[33][34] These lesions are due to direct invasion of epithelial cells.[35] It can also manifest as stromal involvement corresponding to the areas of epithelial pseudodendrites or deep stromal involvement. Isolated stromal involvement is largely an immunological reaction. It may or may not be associated with anterior chamber reaction. Associated trabeculitis manifests as raised intraocular pressure. Corneal sensations decrease significantly after HZO, resulting in recurrent corneal erosions in the chronic phase. The epitheliopathy may result in persistent epithelial defects and subsequent stromal ulceration. The ulcer is called a 'neurotrophic ulcer.'[35]
Thus, the absent terminal bulbs and poor fluorescein uptake by the ulcer base differentiate HZO keratitis from HSV keratitis.
Protozoal Keratitis
Acanthamoeba keratitis: A history of exposure to soil or contaminated water is very often seen in Acanthamoeba keratitis in the developing world. However, in developed countries, contact lens wear has been found to have a strong association with Acanthamoeba keratitis. The spectrum of clinical features can vary from superficial punctate keratitis and pseudo-dendrites to peri-neuritis in the early stages.[36] Ring infiltrates are very characteristically seen in Acanthamoeba keratitis; however, this is not present in all cases.[36] As the disease progresses, the infiltrates extend from anterior to mid to full-thickness infiltrate and become indistinguishable from bacterial and fungal keratitis.[37]
Keratitis by Oomycetes
Pythium keratitis: This keratitis is caused by an oomycete, a distinct phylogenetically related lineage of fungus-like eukaryotic microorganisms. Pythium insidiosum species causes disease in humans. The corneal lesions often mimic fungal infiltrate, and careful examination reveals dry-looking corneal infiltrates denser in the periphery of the whole infiltration with hyphate edges. Pin-head-like lesions and tentacular extensions of the main lesion are very characteristic of Pythium keratitis.[38]
Fungal Keratitis
Microsporidial keratitis: Previously, microsporidia was considered to be a primitive protozoan.[39] However, subsequently, molecular phylogenetic studies revealed that it belonged to fungi.[40][41] Microsporidial keratitis can be classified as 'keratoconjunctivitis' and 'deep stromal keratitis.' The former is more commonly seen in immunocompromised but can also be seen in immunocompetent.[42][43][44] The onset of keratoconjunctivitis is usually acute. A rise in keratoconjunctivitis cases is noted during the rainy season.[45][46] Exposure to muddy water is an important predisposing cause.[47] In keratoconjunctivitis, multiple punctate, coarse, and raised epithelial lesions with stuck-on appearance are noted. During its course, subepithelial infiltrates might appear, mimicking adenoviral keratoconjunctivitis. The conjunctiva shows predominantly follicular response, though papillary reactions are also apparent. Mild anterior chamber reaction with keratic precipitates can be seen.[48] The deep stromal variant has a chronic course of waxing and waning. The stromal infiltrates are deep with intact overlying epithelium. The course can vary from months to years.[49][50]
Filamentous fungal keratitis: A history of trauma with vegetative matter is very often noted. Corneal infiltrates in fungal keratitis are usually dry-looking and have feathery edges with the presence of multiple satellite lesions. Plaque-like (with or without pigmentation) or fungal ball-like surface lesions can also be very commonly seen. At times, the retained corneal vegetative foreign body lies in close association with the infiltrate. Endothelial plaque or exudates in the absence of anterior stromal infiltrate can also be seen. In such a scenario, careful examination often reveals a track from the anterior corneal surface to the endothelium. This track is usually the path of entry for fungal infection and usually follows penetrating trauma. The hypopyon is usually thick and does not shift with a change in head position. The course of the disease is usually longer. Compared to bacterial keratitis, the outcomes of fungal keratitis are poor.[51][52]
Alternaria sp., Bipolaris sp., and Curvularia sp. are the pigmented fungal species causing infections in humans. The infiltrate may have pigmentation (brown) in dematiaceous fungal keratitis.[53]
Candida keratitis: Clinical features are indistinguishable from fungal keratitis.
Onchocerca volvulus keratitis: This results in sclerosing keratitis. Corneal opacity starts from the periphery, and the visual axis gets affected at last. Deep vascularization is noted at 360 degrees.
Non-infectious Keratitis
Local Causes
Trichiatic eyelashes, giant papillae, or any foreign body lodged in the sulcus subtarsalis can result in persistent epithelial denudation mechanically and subsequent stromal ulceration. To start with, these corneal epithelial defects are usually sterile; however, they can get secondarily infected. Ulcers due to trichiatic lashes are very often seen as sequelae of cicatrizing conjunctivitis. The corneal ulcers in trichiatic lashes of the lower lid are usually present in the lower half of the cornea.[54]
Patients with severe allergic conjunctivitis often develop giant papillae and can result in the formation of an ulcer on superior half of cornea called "Shield ulcer." Patients will give a history of previous allergic eye disease.
In both the cases mentioned above, the onset of ulcer development will be gradual.
Patients with a foreign body in the sulcus subtarsalis often have a short history and an acute onset of symptoms. They usually give a history of the foreign body's fall into the eye. On careful examination, multiple linear abrasions in the superior cornea may also be very obvious.[55] Fluorescein stain accentuates the appearance and may show these abrasions clearly.
Systemic Causes
Various systemic causes can alter the local ocular surface milieu and subsequently cause severe dry eye and keratitis.[56] Connective tissue diseases are an important risk factor for keratitis.
Rheumatoid arthritis (RA): RA is known to cause a spectrum of ocular abnormalities. Severe dry eye, scleritis, sclerokeratitis, and peripheral ulcerative keratitis are various manifestations of the disease.[56] A history of small joint pain with or without finger deformities are important clue to reach the diagnosis.[57] If systemic findings are not picked up in time, these cases can end up in corneal perforations or severe systemic disease.
Wegner granulomatosis (WG)/granulomatosis with polyangiitis: WG is a connective tissue disorder (necrotizing vasculitis) that is known to cause keratitis, episcleritis, and scleritis.[58] The patient can present with peripheral ulcerative keratitis.[59][60] A careful examination might reveal a depressed nasal bridge or destruction of the pinna of the ear.[61] History of nasal bleeding and hemoptysis can also be elicited. Here, early diagnosis is important to decrease not only morbidity but also mortality.
Other systemic conditions resulting in keratitis are also known, such as systemic lupus erythematosus, relapsing polychondritis, and polyarteritis nodosa. Careful history-taking helps to diagnose these conditions.
Xerophthalmia: The keratolysis in xerophthalmia results in a punched-out corneal ulcer that has a high propensity to perforate if left untreated.[62] The fellow eye will have a dull and lustreless cornea with conjunctival signs like Bitot's spot and conjunctival xerosis. A history of recent-onset exanthematous fever or diarrhea can be elicited. Other evidence of malnutrition may be present.
Evaluation
Regurgitation on pressure over the lacrimal sac area (ROPLAS) and/or sac syringing constitute an important routine investigation in all corneal ulcer patients to rule out obstructed nasolacrimal duct-induced keratitis. The routine protocol for any corneal ulcer is to look for the characteristic features of the ulcer, followed by corneal scraping to identify the causative organism.[62] The sample is sent for slides and culture with sensitivity. Commonly, two slides are prepared, one each for Gram staining and 10% KOH mount.[63]
The patient is started on medications based on direct microscopy findings, and subsequently, the treatment is further modified based on culture reports. Commonly used culture media are blood and chocolate agar for bacterial growth. Potato dextrose agar and Saboraud's dextrose agar are used for fungal growth and non-nutrient agar with E. coli for Acanthamoeba.[64] Specific microbiological features have been discussed in the management section.
Serology forms the basis for the diagnosis of autoimmune diseases. However, the diagnosis of xerophthalmia is largely clinical.
Treatment / Management
Bacterial Keratitis
For bacterial keratitis, patients are started on fortified topical antibiotics empirically until culture reports are available. Fortified cefazolin 5% or vancomycin and fluoroquinolones or tobramycin or gentamicin give complete coverage against both gram-positive and gram-negative organisms. For keratitis caused by methicillin-resistant Staphylococcus aureus (MRSA), topical vancomycin is the drug of choice.[65] Topical linezolid 0.2% can also be used for MRSA.
Pseudomonas Keratitis: Direct smears on Grams staining show gram-negative rods and culture grows Pseudomonas aeruginosa. The patient is started on topical fluoroquinolones hourly. Treatment is modified once the culture and sensitivity report is available. Oral doxycycline is added to halt the progression of collagenolysis.[66] For resistant strains, topical imipenem-cilastatin (1%) or colistin (0.19%) is being used.[67]
Nocardia Keratitis: Corneal smears are subjected to routine Gram staining and 1% acid-fast staining.[68] Nocardia is a gram-positive, aerobic bacillus with thin beaded filaments exhibiting extensive branching at 90°.[69] Nocardia grows well on conventional culture media, though slower than other organisms. Topical fortified amikacin (2.5%) is the treatment of choice.[15] Pre-treatment with topical steroids worsens the prognosis.[70]
Atypical mycobacteria: Ziehl Neelsen stain is used to identify the organism in smears. Topical fortified amikacin (4%) is the treatment of choice.[18] Clarithromycin (2%) is the second line of management. However, fluoroquinolones (ciprofloxacin 0,3%) can also be used.
Protozoal Keratitis
A clinician needs to have strong suspicion for making a diagnosis of Acanthamoeba keratitis based on the history and clinical features. Previous topical steroid use might increase the yield of the organism in smears and culture; however, it worsens the prognosis. As the clinical picture often mimics viral keratitis, pre-treatment with antivirals may alter the clinical picture. In Gram staining, the cysts are visible as multiple double-walled cysts with inner polyhedral lining. 10% KOH-mount and 10% KOH with 0.1% calcofluor white also demonstrate Acanthamoeba cysts. Non-nutrient agar seeded with E.coli is used for culture. Biguanides and pentamidine are the mainstays of treatment.[71] Polyhexamethylene biguanide (PHMB) (0.02%) and chlorhexidine (0.02%) are commonly used biguanides. Monotherapy with one drug is quite effective. Studies suggest a synergistic effect of biguanide (PHMB and chlorhexidine) and pentamidine. The role of voriconazole and BAK (preservative) is under investigation.[72] The role of endosymbiont bacteria (Pseudomonas aeruginosa) in the development of acanthamoeba keratitis has also been described.[73] The role of the addition of levofloxacin to the anti-protozoal treatment regimen might facilitate treatment in resistant cases.[74] For non-responding cases, deep anterior lamellar keratoplasty is a valid option. For cases with perforation, penetrating keratoplasty is the only option, but with poor prognosis.
Keratitis by Oomycete
Pythium insidiosum on Gram staining and 10% KOH with 0.1% calcofluor white show fungus-like broad aseptate filaments with ribbon-like folds.[38] Zoospore induction helps in identification, and Internal Transcribed Spacer DNA sequencing helps in confirmation.[38] Iodine-potassium-iodide-sulphuric acid stain (IKI-H2SO4) has been described as another way of staining that is said to be exclusive for Pythium insidiosum and may help in early diagnosis.[75] Various studies are being done to establish diagnosis using confocal microscopy; however, results are inconclusive. Hourly administration of topical linezolid (0.2%) along with topical (1% every 2 hours) and oral azithromycin (500mg daily for 3 days in a week) was found to be effective in treating keratitis in the earliest report.[76] The favorable role of these agents in Pythium keratitis was further substantiated by Bagga et al. in their study of these agents over 3 years.[77] However, in-vitro susceptibility of Pythium insidiosum to minocycline and tigecycline was also fairly acceptable.[78]
Fungal Keratitis
Microsporidial keratitis: Microsporodial spores stain well with Grams, silver, and 10% potassium hydroxide (KOH) with 0.1% calcofluor white. The keratoconjunctivitis variant has a self-limiting course.[79] Topical lubricants can be added to palliate the foreign body sensation. Epithelial debridement is also a valid option for the early resolution of corneal lesions.[80] The deep stromal variant is unlikely to respond to conservative management with oral albendazole (400 mg twice daily for 3-4 weeks) and topical fumagillin (topical, 70 mcg/ml, 2 drops every 2 h for 4 days and then 2 drops 4 times daily).[81][82][81] Therapeutic penetrating keratoplasty is the treatment of choice.[50]
Filamentous fungal keratitis: Routine microscopy with 10% KOH alone or 10% KOH with 0.1% calcofluor white reveals hyaline/ pigmented, septate (Aspergillus, Fusarium)/ aseptate (Mucor, Rhizopus) fungal filaments. Preferred culture media for fungal growth are Saboraud's and potato dextrose agar. Topical natamycin (5%) is the drug of choice for filamentous fungal keratitis.[83] Topical voriconazole (1%) is added as an adjunct to natamycin in Aspergillus keratitis, not responding to natamycin alone. Voriconazole is not given as a primary drug for fungal keratitis.[83] Systemic anti-fungal is added for large and deep corneal ulcers. As per the MUTT II trial, the use of oral voriconazole does not make a significant difference compared to placebo in severe fungal keratitis.[84] However, it had some role in Fusarium keratitis.[85] Repeated superficial corneal ulcer debridement is an important component of treatment. Repeated debridement not only decreases fungal load but also facilitates penetration of hydrophilic natamycin into the corneal stroma. The role of intrastromal voriconazole for non-responding lesions cannot be ignored.[86] Topical amphotericin-B (0.15%) is the drug of choice in candida keratitis. Therapeutic penetrating keratoplasty is indicated in keratitis threatening limbus or perforated corneal ulcer not amenable to tissue adhesive application.
Viral Keratitis
Dual staining with Rose-Bengal and fluorescein stain is a very important clinical tool to make a diagnosis of HSV epithelial disease. Fluorescein stain makes the dendrites and geographical ulcers more evident by staining the base of the ulcer, and Rose-Bengal stains the cells at the margin of the ulcer, which are loaded with viruses. The diagnosis of epithelial disease is mostly clinical.[87] Corneal scraping for polymerase chain reaction for HSV viral DNA is done in doubtful cases.[88] Topical antiviral (acyclovir 3%- 5 times a day) is the mainstay of treatment for epithelial disease.[27] For HSV stromal disease and endotheliitis, a topical steroid is the mainstay of treatment. However, oral antiviral (acyclovir 400 mg, 5 times daily) is also added to prevent further recurrence.[89] For HSV necrotizing stromal keratitis, treatment has to be given at the earliest to avoid corneal melt and subsequent perforation. The loading dose of antiviral both topical acyclovir (3%) and oral (acyclovir 400 mg 5 times daily ) is given for the initial three days.[31] Topical steroid is added on the third day. For cases presenting as severe thinning or perforation, tissue adhesive (cyanoacrylate glue) and bandage contact lens are applied. Preferably, a topical steroid is started after applying tissue adhesive to avoid steroid-induced further stromal lysis. For recurrent HSV keratitis, a prophylactic dose of oral antiviral (acyclovir 400 mg twice daily) is given for a year.[90]
The diagnosis of HZO is clinical. The skin lesions associated with corneal dendritiform lesions are very characteristic. Unlike chickenpox lesions, the skin lesions are in the same stage. The ends of dendritiform lesions are tapering, unlike in dendritic ulcers in HSV epithelial keratitis. The pseudodendrites are because of swollen epithelial cells, so they do not take up fluorescein stain. Oral acyclovir (800 mg, 5 times daily for 1 week) is very effective in its treatment in the early stages.[91] The recurrent epithelial erosions should largely be managed with lubricants and prophylactic antibiotics. Neurotrophic ulcers are managed with serum, amniotic membrane transplantation, and tarsorrhaphy. The role of long term prophylaxis with oral antivirals is not clear and needs to be evaluated.[92]
Adenoviral keratitis: The diagnosis of adenoviral keratoconjunctivitis is primarily clinical. However, wherever in doubt, it can be confirmed using PCR techniques. Considering the contagious nature of the disease, maintenance of personal hygiene has a very important role in preventing its transmission. Topical 1% povidone-iodine, in combination with 0.1% dexamethasone, has shown good results.[93] The role of steroids in the early stages is controversial.[20]. Topical cyclosporine 2%, when added in the acute stage in combination with topical steroids, resulted in inhibition of subepithelial infiltrates.[94]
Non-infectious Keratitis
Local Causes
Patients with ulcers related to trichiatic lashes, entropion, or distichiasis need early correction of pathology. The diagnosis is largely clinical. Either electrolysis of eyelash hair root follicle, lid everting procedures, or lid splitting procedures, respectively, need to be done without compromising the gross anatomical relationship.[95][96]
Shield ulcer is an ulcer due to the mechanical effect of giant papillae. Diagnosis is obvious on lid eversion. Topical steroids, along with topical cyclosporine (0.05%) and lubricants, are sufficient enough to control the disease.[97] Control of ocular allergy itself helps improve shield ulcers. Supratarsal triamcinolone injection in refractory cases helps.[98] However, surgical excision of giant papillae and conjunctival autologous graft or mucous membrane graft has also been described in refractory cases.[99][100][95]
Patients with corneal ulcers related to sulcus subtarsalis foreign body needs immediate removal of a foreign body under topical anesthesia either on slit lamp or under the microscope in the operating room.
Systemic Causes
Rheumatoid arthritis: The diagnosis is largely by serological methods; however, clinical findings like finger deformities are suggestive. RA factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) are important serological markers.[57] Anti- CCP antibodies help in making an early diagnosis.[57][101][102] The cause of keratitis is immunological. Topical and oral steroids are the mainstay of initial treatments. The patient is started on oral or subcutaneous methotrexate (steroid-sparing agent) under the rheumatologist's supervision.[103] Perforated corneal ulcers are managed either with cyanoacrylate glue or a multi-layered amniotic membrane graft, provided the perforation is amenable to closure.[104][105] For large perforations, either a corneal patch graft or penetrating keratoplasty with simultaneous immunosuppression is done.[57]
Granulomatosis with polyangiitis: The clinical features are suggestive; however, the serological test is diagnostic. C-ANCA is the serological marker.[106] GPA not only adds to the morbidity but is a life-threatening condition if left untreated.[106] So, early diagnosis and initiation of treatment at the earliest are important. Routine urine examination is also important to look for renal involvement at the presentation—earlier, the renal involvement poorer the prognosis. Pulse cyclophosphamide is the drug of choice.[106] Topical steroids, along with oral immunosuppressive (steroids), can be used to treat peripheral ulcerative keratitis.
Xerophthalmia: Vitamin A supplementation, as per WHO guidelines, needs to be done at the earliest.
Some patients do require surgical interventions, like the application of tissue adhesives, amniotic membrane transplantation, patch graft, or penetrating keratoplasty, to maintain the integrity of the globe. This holds for all keratitis, reaching a fate of severe corneal thinning or perforation. Therapeutic penetrating keratoplasty is planned for limbus threatening infective keratitis.
Apart from various diagnostic and treatment modalities discussed above, now nanoparticles and antimicrobial peptides are being devised for sustained and targeted drug delivery.[107][108] In addition to PCR, genotyping, and confocal microscopy, many other modalities are being worked on.
Differential Diagnosis
Making a diagnosis of keratitis is not difficult; however, finding the etiology is not always easy. Many times, the direct microscopy and culture reports are unremarkable, and the patient has to be treated based on clinical findings. In the early stages, Acanthamoeba keratitis and HSV stromal keratitis are often indistinguishable; however, the late stages of Acanthamoeba keratitis may simulate fungal keratitis.
- Atopic keratoconjunctivitis
- Bacterial endophthalmitis
- Band keratopathy
- Blepharitis
- Corneal ulcer
- Entropion
- Epidemic keratoconjunctivitis
- Fungal keratitis
- Herpes simplex virus keratitis
- Herpes zoster
- Interstitial keratitis
- Neurotrophic keratitis
- Nasolacrimal duct obstruction
- Ocular rosacea
- Pseudophakic bullous keratopathy
- Scleritis
- Viral conjunctivitis
Prognosis
Overall, corneal ulcers take longer to heal. Bacterial ulcers heal relatively earlier than fungal ulcers, and Acanthamoeba keratitis might take months for complete remission. Corneal scarring is the most common outcome following corneal ulcers. These cases can be managed later with glasses, optical iridectomy, or optical keratoplasty to restore vision. Perforated corneal ulcers often tend to have a worse prognosis. The use of prior topical steroids in fungal and Acanthamoeba keratitis worsens the prognosis.
Complications
Complications
- Toxic iridocyclitis
- Secondary glaucoma
- Descemetocele
- Perforation of corneal ulcer
Sequelae of Corneal Perforation
- Iris prolapse
- Anterior dislocation of the lens
- Anterior capsular cataract
- Corneal fistula
- Purulent uveitis
- Intraocular hemorrhage
- Corneal scarring- nebula, macula, leucoma, adherent leucoma
- Keratectasia
- Disorganized anterior chamber
- Autoevisceration
- Phthisis bulbi
Deterrence and Patient Education
Considering the majority of cases of keratitis due to agricultural trauma in developing nations, it is advisable to use eyeshields during harvest season in fields. Apart from these, cases with recurrent HSV keratitis (more than 3 episodes in a year) should take oral antiviral prophylaxis for 1 year.[90]
Pearls and Other Issues
To conclude, comprehensive treatment for keratitis would be first to find the etiology using various clinical and/or microbiological findings and serological markers and then to address it. It can be addressed with topical and/or systemic drugs. In the case where globe integrity is compromised, measures like tissue adhesive application, amniotic membrane transplantation, patch graft, or penetrating keratoplasty are done. Each treatment modality has to be tailored as per the requirement. This article tries to bring out a comprehensive idea about keratitis and its management.
Enhancing Healthcare Team Outcomes
It is always good to have an inhouse microbiologist so that reporting of direct smears can be done at the earliest. Ophthalmologist and a rheumatologist should also work hand in hand. Many patients are referred to a rheumatologist by an ophthalmologist for systemic evaluation and starting immunomodulators. The patients need to follow at both places. An ophthalmologist can suggest a rheumatologist for titrating the dose of immunomodulators based on clinical response. Apart from these, patients are also evaluated for any adverse effect profile. These kinds of work models not only ensure better clinical outcomes and patient safety but also a healthy work atmosphere.
Review Questions
References
- 1.
- Tjia KF, van Putten JP, Pels E, Zanen HC. The interaction between Neisseria gonorrhoeae and the human cornea in organ culture. An electron microscopic study. Graefes Arch Clin Exp Ophthalmol. 1988;226(4):341-5. [PubMed: 3139497]
- 2.
- Mendoza L, Hernandez F, Ajello L. Life cycle of the human and animal oomycete pathogen Pythium insidiosum. J Clin Microbiol. 1993 Nov;31(11):2967-73. [PMC free article: PMC266174] [PubMed: 8263182]
- 3.
- Tondolo JSM, Ledur PC, Loreto ÉS, Verdi CM, Bitencourt PER, de Jesus FPK, Rocha JP, Alves SH, Sassaki GL, Santurio JM. Extraction, characterization and biological activity of a (1,3)(1,6)-β-d-glucan from the pathogenic oomycete Pythium insidiosum. Carbohydr Polym. 2017 Feb 10;157:719-727. [PubMed: 27987983]
- 4.
- Ladas JG, Mondino BJ. Systemic disorders associated with peripheral corneal ulceration. Curr Opin Ophthalmol. 2000 Dec;11(6):468-71. [PubMed: 11141643]
- 5.
- Jeng BH, Gritz DC, Kumar AB, Holsclaw DS, Porco TC, Smith SD, Whitcher JP, Margolis TP, Wong IG. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010 Aug;128(8):1022-8. [PubMed: 20697003]
- 6.
- Srinivasan M, Gonzales CA, George C, Cevallos V, Mascarenhas JM, Asokan B, Wilkins J, Smolin G, Whitcher JP. Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India. Br J Ophthalmol. 1997 Nov;81(11):965-71. [PMC free article: PMC1722056] [PubMed: 9505820]
- 7.
- Hill GM, Ku ES, Dwarakanathan S. Herpes simplex keratitis. Dis Mon. 2014 Jun;60(6):239-46. [PubMed: 24906668]
- 8.
- Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989 Aug;107(8):1160-5. [PubMed: 2757546]
- 9.
- Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007 Nov;33(4):835-54, vii. [PMC free article: PMC2212596] [PubMed: 18037120]
- 10.
- Moore DB, Shirefaw W, Tomkins-Netzer O, Eshete Z, Netzer-Tomkins H, Ben-Zion I. Prevalence of xerophthalmia among malnourished children in rural Ethiopia. Int Ophthalmol. 2013 Oct;33(5):455-9. [PubMed: 23354453]
- 11.
- Kenyon KR. Inflammatory mechanisms in corneal ulceration. Trans Am Ophthalmol Soc. 1985;83:610-63. [PMC free article: PMC1298713] [PubMed: 3914132]
- 12.
- Chigbu DI, Labib BA. Pathogenesis and management of adenoviral keratoconjunctivitis. Infect Drug Resist. 2018;11:981-993. [PMC free article: PMC6054290] [PubMed: 30046247]
- 13.
- Dana MR, Qian Y, Hamrah P. Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea. 2000 Sep;19(5):625-43. [PubMed: 11009315]
- 14.
- DeCroos FC, Garg P, Reddy AK, Sharma A, Krishnaiah S, Mungale M, Mruthyunjaya P., Hyderabad Endophthalmitis Research Group. Optimizing diagnosis and management of nocardia keratitis, scleritis, and endophthalmitis: 11-year microbial and clinical overview. Ophthalmology. 2011 Jun;118(6):1193-200. [PubMed: 21276615]
- 15.
- Sridhar MS, Gopinathan U, Garg P, Sharma S, Rao GN. Ocular nocardia infections with special emphasis on the cornea. Surv Ophthalmol. 2001 Mar-Apr;45(5):361-78. [PubMed: 11274691]
- 16.
- Ko J, Kim SK, Yong DE, Kim TI, Kim EK. Delayed onset Mycobacterium intracellulare keratitis after laser in situ keratomileusis: A case report and literature review. Medicine (Baltimore). 2017 Dec;96(51):e9356. [PMC free article: PMC5758224] [PubMed: 29390522]
- 17.
- John T, Velotta E. Nontuberculous (atypical) mycobacterial keratitis after LASIK: current status and clinical implications. Cornea. 2005 Apr;24(3):245-55. [PubMed: 15778593]
- 18.
- Moorthy RS, Valluri S, Rao NA. Nontuberculous mycobacterial ocular and adnexal infections. Surv Ophthalmol. 2012 May-Jun;57(3):202-35. [PubMed: 22516536]
- 19.
- Kheir WJ, Sheheitli H, Abdul Fattah M, Hamam RN. Nontuberculous Mycobacterial Ocular Infections: A Systematic Review of the Literature. Biomed Res Int. 2015;2015:164989. [PMC free article: PMC4461732] [PubMed: 26106601]
- 20.
- Omari AA, Mian SI. Adenoviral keratitis: a review of the epidemiology, pathophysiology, clinical features, diagnosis, and management. Curr Opin Ophthalmol. 2018 Jul;29(4):365-372. [PubMed: 29708932]
- 21.
- Mader TH, Stulting RD. Viral keratitis. Infect Dis Clin North Am. 1992 Dec;6(4):831-49. [PubMed: 1334105]
- 22.
- Bialasiewicz A. Adenoviral keratoconjunctivitis. Sultan Qaboos Univ Med J. 2007 Apr;7(1):15-23. [PMC free article: PMC3086413] [PubMed: 21654940]
- 23.
- Akkaya S, Ozkurt YB. Persistent Symblepharon in an Infant Following Epidemic Keratoconjunctivitis. Med Hypothesis Discov Innov Ophthalmol. 2016 Fall;5(3):74-77. [PMC free article: PMC5347208] [PubMed: 28293652]
- 24.
- Hammer LH, Perry HD, Donnenfeld ED, Rahn EK. Symblepharon formation in epidemic keratoconjunctivitis. Cornea. 1990 Oct;9(4):338-40. [PubMed: 2078963]
- 25.
- Shoji J, Sakimoto T, Inada N, Kamei Y, Matsubara M, Takamura E, Sawa M. A diagnostic method for herpes simplex keratitis by simultaneous measurement of viral DNA and virus-specific secretory IgA in tears: an evaluation. Jpn J Ophthalmol. 2016 Jul;60(4):294-301. [PubMed: 27126382]
- 26.
- Chang EJ, Dreyer EB. Herpesvirus infections of the anterior segment. Int Ophthalmol Clin. 1996 Summer;36(3):17-28. [PubMed: 8989597]
- 27.
- Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015 Jan 09;1(1):CD002898. [PMC free article: PMC4443501] [PubMed: 25879115]
- 28.
- Souza PM, Holland EJ, Huang AJ. Bilateral herpetic keratoconjunctivitis. Ophthalmology. 2003 Mar;110(3):493-6. [PubMed: 12623810]
- 29.
- Holbach LM, Font RL, Naumann GO. Herpes simplex stromal and endothelial keratitis. Granulomatous cell reactions at the level of Descemet's membrane, the stroma, and Bowman's layer. Ophthalmology. 1990 Jun;97(6):722-8. [PubMed: 2165231]
- 30.
- McGill J. The enigma of herpes stromal disease. Br J Ophthalmol. 1987 Feb;71(2):118-25. [PMC free article: PMC1041102] [PubMed: 3548807]
- 31.
- Dutt S, Acharya M, Gour A, Sapra N, Chauhan L, Mathur U. Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis. Indian J Ophthalmol. 2016 Apr;64(4):292-5. [PMC free article: PMC4901847] [PubMed: 27221681]
- 32.
- Kalogeropoulos CD, Bassukas ID, Moschos MM, Tabbara KF. Eye and Periocular Skin Involvement in Herpes Zoster Infection. Med Hypothesis Discov Innov Ophthalmol. 2015 Winter;4(4):142-156. [PMC free article: PMC5087099] [PubMed: 27800502]
- 33.
- Li JY. Herpes zoster ophthalmicus: acute keratitis. Curr Opin Ophthalmol. 2018 Jul;29(4):328-333. [PubMed: 29794881]
- 34.
- Hu AY, Strauss EC, Holland GN, Chan MF, Yu F, Margolis TP. Late varicella-zoster virus dendriform keratitis in patients with histories of herpes zoster ophthalmicus. Am J Ophthalmol. 2010 Feb;149(2):214-220.e3. [PMC free article: PMC4507370] [PubMed: 19909942]
- 35.
- Davis AR, Sheppard J. Herpes Zoster Ophthalmicus Review and Prevention. Eye Contact Lens. 2019 Sep;45(5):286-291. [PubMed: 30844951]
- 36.
- Maycock NJ, Jayaswal R. Update on Acanthamoeba Keratitis: Diagnosis, Treatment, and Outcomes. Cornea. 2016 May;35(5):713-20. [PubMed: 26989955]
- 37.
- Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite. 2015;22:10. [PMC free article: PMC4330640] [PubMed: 25687209]
- 38.
- Sharma S, Balne PK, Motukupally SR, Das S, Garg P, Sahu SK, Arunasri K, Manjulatha K, Mishra DK, Shivaji S. Pythium insidiosum keratitis: clinical profile and role of DNA sequencing and zoospore formation in diagnosis. Cornea. 2015 Apr;34(4):438-42. [PubMed: 25738236]
- 39.
- Vossbrinck CR, Maddox JV, Friedman S, Debrunner-Vossbrinck BA, Woese CR. Ribosomal RNA sequence suggests microsporidia are extremely ancient eukaryotes. 1987 Mar 26-Apr 1Nature. 326(6111):411-4. [PubMed: 3550472]
- 40.
- Weiss LM, Edlind TD, Vossbrinck CR, Hashimoto T. Microsporidian molecular phylogeny: the fungal connection. J Eukaryot Microbiol. 1999 Sep-Oct;46(5):17S-18S. [PubMed: 10519229]
- 41.
- Capella-Gutiérrez S, Marcet-Houben M, Gabaldón T. Phylogenomics supports microsporidia as the earliest diverging clade of sequenced fungi. BMC Biol. 2012 May 31;10:47. [PMC free article: PMC3586952] [PubMed: 22651672]
- 42.
- Sridhar MS, Sharma S. Microsporidial keratoconjunctivitis in a HIV-seronegative patient treated with debridement and oral itraconazole. Am J Ophthalmol. 2003 Oct;136(4):745-6. [PubMed: 14516821]
- 43.
- Joseph J, Sridhar MS, Murthy S, Sharma S. Clinical and microbiological profile of microsporidial keratoconjunctivitis in southern India. Ophthalmology. 2006 Apr;113(4):531-7. [PubMed: 16488011]
- 44.
- Moon SJ, Mann PM, Matoba AY. Microsporidial keratoconjunctivitis in a healthy patient with a history of LASIK surgery. Cornea. 2003 Apr;22(3):271-2. [PubMed: 12658099]
- 45.
- Das S, Sharma S, Sahu SK, Nayak SS, Kar S. New microbial spectrum of epidemic keratoconjunctivitis: clinical and laboratory aspects of an outbreak. Br J Ophthalmol. 2008 Jun;92(6):861-2. [PubMed: 18523092]
- 46.
- Reddy AK, Balne PK, Garg P, Krishnaiah S. Is microsporidial keratitis a seasonal infection in India? Clin Microbiol Infect. 2011 Jul;17(7):1114-6. [PubMed: 21726353]
- 47.
- Loh RS, Chan CM, Ti SE, Lim L, Chan KS, Tan DT. Emerging prevalence of microsporidial keratitis in Singapore: epidemiology, clinical features, and management. Ophthalmology. 2009 Dec;116(12):2348-53. [PubMed: 19815287]
- 48.
- Tung-Lien Quek D, Pan JC, Krishnan PU, Zhao PS, Teoh SC. Microsporidial keratoconjunctivitis in the tropics: a case series. Open Ophthalmol J. 2011;5:42-7. [PMC free article: PMC3104614] [PubMed: 21643428]
- 49.
- Pinnolis M, Egbert PR, Font RL, Winter FC. Nosematosis of the cornea. Case report, including electron microscopic studies. Arch Ophthalmol. 1981 Jun;99(6):1044-7. [PubMed: 6786272]
- 50.
- Vemuganti GK, Garg P, Sharma S, Joseph J, Gopinathan U, Singh S. Is microsporidial keratitis an emerging cause of stromal keratitis? A case series study. BMC Ophthalmol. 2005 Aug 17;5:19. [PMC free article: PMC1200253] [PubMed: 16105181]
- 51.
- Wong TY, Ng TP, Fong KS, Tan DT. Risk factors and clinical outcomes between fungal and bacterial keratitis: a comparative study. CLAO J. 1997 Oct;23(4):275-81. [PubMed: 9348453]
- 52.
- Lalitha P, Prajna NV, Kabra A, Mahadevan K, Srinivasan M. Risk factors for treatment outcome in fungal keratitis. Ophthalmology. 2006 Apr;113(4):526-30. [PubMed: 16581414]
- 53.
- Garg P, Gopinathan U, Choudhary K, Rao GN. Keratomycosis: clinical and microbiologic experience with dematiaceous fungi. Ophthalmology. 2000 Mar;107(3):574-80. [PubMed: 10711898]
- 54.
- Rice NS, Jones BR. Vernal kerato-conjunctivitis: an allergic disease of the eyes of children. Clin Allergy. 1973 Dec;3 Suppl:629-37. [PubMed: 4220246]
- 55.
- Bhalerao SA, Singh P, Rani PK, Rathi V. The sting of a honey bee: An unusual subconjunctival foreign body. Indian J Ophthalmol. 2017 Nov;65(11):1226-1228. [PMC free article: PMC5700603] [PubMed: 29133661]
- 56.
- Itty S, Pulido JS, Bakri SJ, Baratz KH, Matteson EL, Hodge DO. Anti-cyclic citrullinated peptide, rheumatoid factor, and ocular symptoms typical of rheumatoid arthritis. Trans Am Ophthalmol Soc. 2008;106:75-81; discussion 81-3. [PMC free article: PMC2646447] [PubMed: 19277223]
- 57.
- Singh P, Kumar A, Chandra P. Rheumatoid factor versus anti - cyclic citrullinated peptide antibody as screening tool for rheumatoid arthritis in an ophthalmic clinic. Indian J Ophthalmol. 2020 Jan;68(1):236-238. [PMC free article: PMC6951140] [PubMed: 31856537]
- 58.
- Bullen CL, Liesegang TJ, McDonald TJ, DeRemee RA. Ocular complications of Wegener's granulomatosis. Ophthalmology. 1983 Mar;90(3):279-90. [PubMed: 6602963]
- 59.
- Cao Y, Zhang W, Wu J, Zhang H, Zhou H. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment. J Ophthalmol. 2017;2017:7298026. [PMC free article: PMC5530438] [PubMed: 28785483]
- 60.
- Říhová E, Svozílková P, Brichová M, Klímová A, Kuthan P, Diblík P. Ocular Manifestations of Granulomatosis with Polyangiitis. Cesk Slov Oftalmol. 2019 Spring;74(5):167-174. [PubMed: 31234629]
- 61.
- Bluestone R. Bridge collapse followed by joint pains, nephritis. Hosp Pract (Off Ed). 1983 Aug;18(8):58L, 58P. [PubMed: 6409795]
- 62.
- Khor WB, Prajna VN, Garg P, Mehta JS, Xie L, Liu Z, Padilla MDB, Joo CK, Inoue Y, Goseyarakwong P, Hu FR, Nishida K, Kinoshita S, Puangsricharern V, Tan AL, Beuerman R, Young A, Sharma N, Haaland B, Mah FS, Tu EY, Stapleton FJ, Abbott RL, Tan DT., ACSIKS Group. The Asia Cornea Society Infectious Keratitis Study: A Prospective Multicenter Study of Infectious Keratitis in Asia. Am J Ophthalmol. 2018 Nov;195:161-170. [PubMed: 30098351]
- 63.
- Gupta N, Tandon R. Investigative modalities in infectious keratitis. Indian J Ophthalmol. 2008 May-Jun;56(3):209-13. [PMC free article: PMC2636118] [PubMed: 18417821]
- 64.
- Garg P. Investigative modalities in infectious keratitis. Indian J Ophthalmol. 2009 Mar-Apr;57(2):159. [PMC free article: PMC2684419] [PubMed: 19237797]
- 65.
- Sharma V, Sharma S, Garg P, Rao GN. Clinical resistance of Staphylococcus keratitis to ciprofloxacin monotherapy. Indian J Ophthalmol. 2004 Dec;52(4):287-92. [PubMed: 15693319]
- 66.
- McElvanney AM. Doxycycline in the management of pseudomonas corneal melting: two case reports and a review of the literature. Eye Contact Lens. 2003 Oct;29(4):258-61. [PubMed: 14555906]
- 67.
- Chatterjee S, Agrawal D. Multi-drug resistant Pseudomonas aeruginosa keratitis and its effective treatment with topical colistimethate. Indian J Ophthalmol. 2016 Feb;64(2):153-7. [PMC free article: PMC4850814] [PubMed: 27050354]
- 68.
- Garg P. Fungal, Mycobacterial, and Nocardia infections and the eye: an update. Eye (Lond). 2012 Feb;26(2):245-51. [PMC free article: PMC3272218] [PubMed: 22173077]
- 69.
- Sridhar MS, Sharma S, Reddy MK, Mruthyunjay P, Rao GN. Clinicomicrobiological review of Nocardia keratitis. Cornea. 1998 Jan;17(1):17-22. [PubMed: 9436875]
- 70.
- Lalitha P, Srinivasan M, Rajaraman R, Ravindran M, Mascarenhas J, Priya JL, Sy A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Lietman TM, Acharya NR. Nocardia keratitis: clinical course and effect of corticosteroids. Am J Ophthalmol. 2012 Dec;154(6):934-939.e1. [PMC free article: PMC3498612] [PubMed: 22959881]
- 71.
- Lorenzo-Morales J, Martín-Navarro CM, López-Arencibia A, Arnalich-Montiel F, Piñero JE, Valladares B. Acanthamoeba keratitis: an emerging disease gathering importance worldwide? Trends Parasitol. 2013 Apr;29(4):181-7. [PubMed: 23433689]
- 72.
- Tu EY, Shoff ME, Gao W, Joslin CE. Effect of low concentrations of benzalkonium chloride on acanthamoebal survival and its potential impact on empirical therapy of infectious keratitis. JAMA Ophthalmol. 2013 May;131(5):595-600. [PMC free article: PMC7430836] [PubMed: 23519403]
- 73.
- Nakagawa H, Hattori T, Koike N, Ehara T, Narimatsu A, Kumakura S, Matsumoto T, Goto H. Number of Bacteria and Time of Coincubation With Bacteria Required for the Development of Acanthamoeba Keratitis. Cornea. 2017 Mar;36(3):353-357. [PubMed: 28079686]
- 74.
- Nakagawa H, Hattori T, Koike N, Ehara T, Fujita K, Takahashi H, Kumakura S, Kuroda M, Matsumoto T, Goto H. Investigation of the Role of Bacteria in the Development of Acanthamoeba Keratitis. Cornea. 2015 Oct;34(10):1308-15. [PubMed: 26203748]
- 75.
- Mittal R, Jena SK, Desai A, Agarwal S. Pythium Insidiosum Keratitis: Histopathology and Rapid Novel Diagnostic Staining Technique. Cornea. 2017 Sep;36(9):1124-1132. [PubMed: 28582375]
- 76.
- Ramappa M, Nagpal R, Sharma S, Chaurasia S. Successful Medical Management of Presumptive Pythium insidiosum Keratitis. Cornea. 2017 Apr;36(4):511-514. [PubMed: 28207431]
- 77.
- Bagga B, Sharma S, Madhuri Guda SJ, Nagpal R, Joseph J, Manjulatha K, Mohamed A, Garg P. Leap forward in the treatment of Pythium insidiosum keratitis. Br J Ophthalmol. 2018 Dec;102(12):1629-1633. [PubMed: 29545414]
- 78.
- Loreto ES, Tondolo JS, Pilotto MB, Alves SH, Santurio JM. New insights into the in vitro susceptibility of Pythium insidiosum. Antimicrob Agents Chemother. 2014 Dec;58(12):7534-7. [PMC free article: PMC4249561] [PubMed: 25223997]
- 79.
- Sanjay S. Clinical trial of 0.02% polyhexamethylene biguanide versus placebo in the treatment of microsporidial keratoconjunctivitis. Am J Ophthalmol. 2011 Jan;151(1):183; author reply 183. [PubMed: 21163375]
- 80.
- Das S, Wallang BS, Sharma S, Bhadange YV, Balne PK, Sahu SK. The efficacy of corneal debridement in the treatment of microsporidial keratoconjunctivitis: a prospective randomized clinical trial. Am J Ophthalmol. 2014 Jun;157(6):1151-5. [PubMed: 24589573]
- 81.
- Font RL, Samaha AN, Keener MJ, Chevez-Barrios P, Goosey JD. Corneal microsporidiosis. Report of case, including electron microscopic observations. Ophthalmology. 2000 Sep;107(9):1769-75. [PubMed: 10964843]
- 82.
- Didier ES, Maddry JA, Brindley PJ, Stovall ME, Didier PJ. Therapeutic strategies for human microsporidia infections. Expert Rev Anti Infect Ther. 2005 Jun;3(3):419-34. [PubMed: 15954858]
- 83.
- Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, Raghavan A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Porco TC, Acharya NR, Lietman TM., Mycotic Ulcer Treatment Trial Group. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. 2013 Apr;131(4):422-9. [PMC free article: PMC3769211] [PubMed: 23710492]
- 84.
- Prajna NV, Krishnan T, Rajaraman R, Patel S, Srinivasan M, Das M, Ray KJ, O'Brien KS, Oldenburg CE, McLeod SD, Zegans ME, Porco TC, Acharya NR, Lietman TM, Rose-Nussbaumer J., Mycotic Ulcer Treatment Trial II Group. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial. JAMA Ophthalmol. 2016 Dec 01;134(12):1365-1372. [PMC free article: PMC6044431] [PubMed: 27787540]
- 85.
- Prajna NV, Krishnan T, Rajaraman R, Patel S, Shah R, Srinivasan M, Devi L, Das M, Ray KJ, O'Brien KS, Oldenburg CE, McLeod SD, Zegans ME, Acharya NR, Lietman TM, Rose-Nussbaumer J., Mycotic Ulcer Treatment Trial Group. Adjunctive Oral Voriconazole Treatment of Fusarium Keratitis: A Secondary Analysis From the Mycotic Ulcer Treatment Trial II. JAMA Ophthalmol. 2017 Jun 01;135(6):520-525. [PMC free article: PMC5847083] [PubMed: 28426856]
- 86.
- Sharma N, Sahay P, Maharana PK, Singhal D, Saluja G, Bandivadekar P, Chako J, Agarwal T, Sinha R, Titiyal JS, Satpathy G, Velpandian T. Management Algorithm for Fungal Keratitis: The TST (Topical, Systemic, and Targeted Therapy) Protocol. Cornea. 2019 Feb;38(2):141-145. [PubMed: 30334872]
- 87.
- Darougar S, Wishart MS, Viswalingam ND. Epidemiological and clinical features of primary herpes simplex virus ocular infection. Br J Ophthalmol. 1985 Jan;69(1):2-6. [PMC free article: PMC1040512] [PubMed: 3965025]
- 88.
- Koizumi N, Nishida K, Adachi W, Tei M, Honma Y, Dota A, Sotozono C, Yokoi N, Yamamoto S, Kinoshita S. Detection of herpes simplex virus DNA in atypical epithelial keratitis using polymerase chain reaction. Br J Ophthalmol. 1999 Aug;83(8):957-60. [PMC free article: PMC1723153] [PubMed: 10413702]
- 89.
- Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000 Aug;118(8):1030-6. [PubMed: 10922194]
- 90.
- Wu X, Chen X. Acyclovir for the treatment and prevention of recurrent infectious herpes simplex keratitis. Chin Med J (Engl). 2002 Oct;115(10):1569-72. [PubMed: 12490113]
- 91.
- Hoang-Xuan T, Büchi ER, Herbort CP, Denis J, Frot P, Thénault S, Pouliquen Y. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology. 1992 Jul;99(7):1062-70; discussion 1070-1. [PubMed: 1495785]
- 92.
- Reichstein JB, Patel V, Mekaroonkamol P, Dacha S, Keilin SA, Cai Q, Willingham FF. Practice Patterns and Use of Endoscopic Retrograde Cholangiopancreatography in the Management of Recurrent Acute Pancreatitis. Clin Endosc. 2020 Jan;53(1):73-81. [PMC free article: PMC7003016] [PubMed: 31273969]
- 93.
- Kovalyuk N, Kaiserman I, Mimouni M, Cohen O, Levartovsky S, Sherbany H, Mandelboim M. Treatment of adenoviral keratoconjunctivitis with a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study. Acta Ophthalmol. 2017 Dec;95(8):e686-e692. [PubMed: 28342227]
- 94.
- Asena L, Şıngar Özdemir E, Burcu A, Ercan E, Çolak M, Altınörs DD. Comparison of clinical outcome with different treatment regimens in acute adenoviral keratoconjunctivitis. Eye (Lond). 2017 May;31(5):781-787. [PMC free article: PMC5437338] [PubMed: 28157224]
- 95.
- Sakarya Y, Sakarya R, Yildirim A. Electrolysis treatment of trichiasis by using ultra-fine needle. Eur J Ophthalmol. 2010 Jul-Aug;20(4):664-8. [PubMed: 20037913]
- 96.
- Anderson RL, Harvey JT. Lid splitting and posterior lamella cryosurgery for congenital and acquired distichiasis. Arch Ophthalmol. 1981 Apr;99(4):631-4. [PubMed: 7224935]
- 97.
- Kumar S. Combined therapy for vernal shield ulcer. Clin Exp Optom. 2008 Jan;91(1):111-4. [PubMed: 18045257]
- 98.
- Singh S, Pal V, Dhull CS. Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis. Indian J Ophthalmol. 2001 Dec;49(4):241-5. [PubMed: 12930116]
- 99.
- Nishiwaki-Dantas MC, Dantas PE, Pezzutti S, Finzi S. Surgical resection of giant papillae and autologous conjunctival graft in patients with severe vernal keratoconjunctivitis and giant papillae. Ophthalmic Plast Reconstr Surg. 2000 Nov;16(6):438-42. [PubMed: 11106188]
- 100.
- Iyer G, Agarwal S, Srinivasan B. Outcomes and Rationale of Excision and Mucous Membrane Grafting in Palpebral Vernal Keratoconjunctivitis. Cornea. 2018 Feb;37(2):172-176. [PubMed: 29040121]
- 101.
- El-Banna H, Jiman-Fatani A. Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis. BMC Musculoskelet Disord. 2014 Nov 19;15:379. [PMC free article: PMC4247608] [PubMed: 25406539]
- 102.
- Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004 Feb;50(2):380-6. [PubMed: 14872479]
- 103.
- Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc. 2013;124:16-25. [PMC free article: PMC3715949] [PubMed: 23874006]
- 104.
- Bernauer W, Ficker LA, Watson PG, Dart JK. The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes. Ophthalmology. 1995 Sep;102(9):1325-37. [PubMed: 9097770]
- 105.
- Lohchab M, Prakash G, Arora T, Maharana P, Jhanji V, Sharma N, Vajpayee RB. Surgical management of peripheral corneal thinning disorders. Surv Ophthalmol. 2019 Jan-Feb;64(1):67-78. [PubMed: 29886126]
- 106.
- Tarabishy AB, Schulte M, Papaliodis GN, Hoffman GS. Wegener's granulomatosis: clinical manifestations, differential diagnosis, and management of ocular and systemic disease. Surv Ophthalmol. 2010 Sep-Oct;55(5):429-44. [PubMed: 20638092]
- 107.
- De Coupade C, Fittipaldi A, Chagnas V, Michel M, Carlier S, Tasciotti E, Darmon A, Ravel D, Kearsey J, Giacca M, Cailler F. Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules. Biochem J. 2005 Sep 01;390(Pt 2):407-18. [PMC free article: PMC1198920] [PubMed: 15859953]
- 108.
- Brandt CR. Peptide therapeutics for treating ocular surface infections. J Ocul Pharmacol Ther. 2014 Nov;30(9):691-9. [PMC free article: PMC4220699] [PubMed: 25250986]
Disclosure: Prabhakar Singh declares no relevant financial relationships with ineligible companies.
Disclosure: Abhishek Gupta declares no relevant financial relationships with ineligible companies.
Disclosure: Koushik Tripathy declares no relevant financial relationships with ineligible companies.
- Continuing Education Activity
- Introduction
- Etiology
- Epidemiology
- Pathophysiology
- Histopathology
- History and Physical
- Evaluation
- Treatment / Management
- Differential Diagnosis
- Prognosis
- Complications
- Deterrence and Patient Education
- Pearls and Other Issues
- Enhancing Healthcare Team Outcomes
- Review Questions
- References
- Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection.[J Virol. 2019]Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection.Montgomery ML, Callegan MC, Fuller KK, Carr DJJ. J Virol. 2019 Aug 15; 93(16). Epub 2019 Jul 30.
- Cornea Transplantation.[StatPearls. 2024]Cornea Transplantation.Maghsoudlou P, Sood G, Gurnani B, Akhondi H. StatPearls. 2024 Jan
- Challenges in the management of Neisseria gonorrhoeae keratitis.[Int Ophthalmol. 2015]Challenges in the management of Neisseria gonorrhoeae keratitis.McElnea E, Stapleton P, Khan S, Stokes J, Higgins G. Int Ophthalmol. 2015 Feb; 35(1):135-40. Epub 2014 Dec 30.
- Review Keratitis.[Biosci Rep. 2001]Review Keratitis.Sharma S. Biosci Rep. 2001 Aug; 21(4):419-44.
- Review Contact lens related corneal infections.[Biosci Rep. 2001]Review Contact lens related corneal infections.Willcox MD, Holden BA. Biosci Rep. 2001 Aug; 21(4):445-61.
- Keratitis - StatPearlsKeratitis - StatPearls
Your browsing activity is empty.
Activity recording is turned off.
See more...