Keratitis

Clinical classification of keratitis [1, 2]: I. By etiology:

A. Exogenous keratitis 1. Corneal erosions. 2. Traumatic keratitis caused by mechanical, physical, or chemical trauma. 3. Infectious keratitis of bacterial origin. 4. Keratitis caused by diseases of the conjunctiva, eyelids, meibomian glands. 5. Fungal keratitis or keratomycosis.

B. Endogenous keratitis 1. Infectious keratitis: – tuberculous; – syphilitic; – herpetic; – hematogenous (deep diffuse keratitis, deep limited keratitis, sclerosing keratitis);

2

• allergic (phlyctenular keratitis, fascicular or wandering keratitis, pannus phlyctenular keratitis). 2. Neuroparalytic keratitis. 3. Avitaminosis keratitis. 4. Acanthamoeba lesions

C. Keratitis of unknown etiology. II. By course: - acute - subacute - chronic - recurrent

Diagnostic and treatment algorithm: determination of the etiology of the process based on medical history data, clinical presentation, laboratory test results*

CLINICAL PROTOCOL FOR DIAGNOSIS AND TREATMENT

METHODS, APPROACHES AND DIAGNOSTIC PROCEDURES:

Complaints:

• lacrimation;
• photophobia;
• foreign body sensation;
• decreased vision;
• pain syndrome.

History:

• indications of previous trauma;
• foreign body entry/removal;
• contact lens use;
• previous acute respiratory viral infections, infectious and other diseases;
• non-compliance with hygiene.

Physical examinations: not informative

Laboratory examinations*: bacteriological culture from the conjunctival cavity with identification of the pathogen and determination of antibiotic sensitivity in bacterial keratitis, on Sabouraud medium – in ophthalmomycoses.

*In viral, neurotrophic, acanthamoeba keratitis, the diagnosis is made based on typical clinical presentation and history. Bacteriological culture in the absence of discharge, signs of secondary bacterial infection (mixed infection) – is not required.

Instrumental studies:

Visometry:

• low visual acuity / absence of vision, with ineffectiveness of optical correction – with central localization of infiltrate;
• visual acuity may not change with peripheral localization of infiltrate

Biomicroscopy:

• presence or absence of discharge in the conjunctival cavity;
• presence, size of de-epithelialization;
• presence, intensity of corneal edema;
• presence, localization, depth, edge character, color of infiltrate;
• presence/absence of ulceration;
• absence/presence of newly formed vessels – depth, localization;
• anterior chamber – presence, size, aqueous humor of anterior chamber;
• pupil condition, size, photoreaction;
• lens condition, vitreous body*;
• reflex from fundus, fundus*;
• with peripheral localization of the process with possibility of visualization of the pupillary zone and deeper media.

Tonometry:

• intraocular pressure within normal limits / elevated in concomitant glaucoma. Measured non-contact (transpalpebral, by palpation)

Keratopachymetry:

• presence of local / diffuse corneal edema – increase in corneal thickness over 500-600 μm in the central zone;
• presence of thinning – decrease in corneal thickness less than 450 μm

Medication treatment: etiotropic therapy in case of established microflora and sensitivity or according to clinical presentation: antibacterial, antiviral, antifungal, kerato-protective, tear replacement drugs, mydriatics.

List of essential medicines (having 100% probability of use) Drug group, international nonproprietary name, Method of administration, Level of evidence Antimicrobial drug Levofloxacin drops Instillations in

Approved by the Joint Commission on Quality of Medical Services of the Ministry of Health

of the Republic of Kazakhstan on February 28, 2019

Protocol No. 55

KERATITIS

INTRODUCTORY PART 1.1 ICD-10 and 9 Code(s):

ICD-10 Code Name H 16.0 Keratitis

H 16.1 H 16.3

H 16.8

Other superficial keratitis without conjunctivitis Interstitial (stromal) and deep keratitis Other forms of keratitis

ICD-9

Phototherapeutic

keratectomy (PTK)

Corneal collagen

cross-linking H 16.9 Keratitis, unspecified 1.2 Date of protocol development/revision: 2014 (revision 2018)

Abbreviations used in the protocol: ELISA – enzyme-linked immunosorbent assay HSV – herpes simplex virus CMV – cytomegalovirus ARVI – acute respiratory viral infection CL – contact lens SCL – soft contact lens agr. – agricultural US – ultrasound examination EPI – electrophysiological investigations PTK – phototherapeutic keratectomy

Protocol users: ophthalmologists, general practitioners. 1.5 Patient category: adults. 1.6 Evidence level scale:

A High-quality meta-analysis, systematic review of RCTs or large RCT with very low probability (++) of systematic error, the results of which can be applied to the relevant population.

B High-quality (++) systematic review of cohort or case-control studies or high-quality (++) cohort or case-control studies with very low risk of systematic error or RCT with low (+) risk of systematic error, the results of which can be applied to the relevant population.

C Cohort or case-control study or controlled study without randomization with low risk of systematic error (+). The results of which can be applied to the relevant population or RCT with very low or low risk of systematic error (++ or +), the results of which cannot be directly applied to the relevant population.

D Case series description or uncontrolled study or expert opinion.

etiotropic drug therapy, mydriatics

keratoprotective, tear replacement therapy for 1-3 months after clinical recovery _______________________________________________________________________ * Note: bacterial culture results are possible on days 3-7 depending on laboratory equipment. Negative bacterial culture in infectious corneal ulcers is acceptable in 40-80% of cases. Non-infectious ulcers may become infected with secondary infection. bacteriological culture from the conjunctival cavity with determination of antibiotic sensitivity; bacteriological culture from the conjunctival cavity on Sabouraud medium for diagnosis of ophthalmomycosis with sensitivity determination; microscopic examination of conjunctival discharge for diagnosis of ophthalmomycosis. Determination of Ig G to herpes simplex viruses, cytomegalovirus by ELISA method

5

Differential diagnosis and justification for additional investigations:

History

Severity of corneal syndrome Infiltrate characteristics

Corneal sensitivity Laboratory investigations Exogenous keratitis Bacterial infection with non-compliance with hygiene, trauma, foreign body entry/removal Herpetic

preceding ARVI, hypothermia, stress, climate change, general decrease in immunity

Fungal

Any agr. trauma; entry into the eye of wood, plants, soil; patient's stay in bathhouse. Hormonal disorders in women.

sharply pronounced

-

preserved positive bacterial culture on standard media may be absent dendritic geographic disciform

reduced / absent positive ELISA tests for HSV

moderately pronounced

white, with diffuse edge, "crumb-like" "cottage cheese-like", with indistinct borders preserved

positive bacterial culture on Sabouraud medium

Acanthamoeba Endogenous keratitis Neurotrophic keratitis

contact lens wear; violation of CL use regimen: including nighttime, contact with tap water, pool, bathhouse, water body.

sharply pronounced ring-shaped

previous or existing infectious diseases, general somatic diseases

moderately pronounced deep stromal, with early deep neovascularization

neurological pathology: previous stroke, neuritis, lesions of facial, trigeminal nerve, neurosurgical history may be absent

-

may be reduced - preserved

positive blood tests for specific infections, markers reduced / absent

6

TREATMENT TACTICS AT OUTPATIENT LEVEL: 1. Drug therapy: relief of inflammatory process, corneal edema, infiltrate resorption, achievement of complete epithelialization, vision improvement, elimination of corneal perforation threat.

SCL for the purpose of corneal epithelialization in recurrent, long-lasting erosion, de-epithelialization.

Drug treatment: keratoprotective therapy. Algorithm for treatment of corneal erosion:

Forced instillations – for 30 min. Sulfacyl sodium* 30% (adults),

Sulfacyl sodium* 20% (children/adults with severe pain syndrome). Upon completion of instillations – apply dexpanthenol (Corneregel) into the conjunctival cavity, 30-40 minutes – with eyes closed. 2 times a day – 3 days, 1 time a day – 3 days

Positive dynamics: reduction of erosion /complete

epithelialization Absence of dynamics: erosion size

remains unchanged

Extensive erosion in the optical zone

SCL**

Tear preparations 2 drops 6 times a day – 2 weeks, 4 times a day – 2

__________m_o_nt_h_s_(d_e_p_en_d_in_g _o_n _d_yn_a_m_ic_s_)________________________________ *In the presence of SCL, sulfacyl sodium instillations are not advisable.

**SCL – silicone-hydrogel, extended wear, with replacement every 2-3 weeks. In the presence of signs of secondary infection, infiltrate – SCL replacement every 7-10 days + antibiotic instillations 6 times a day – 7-10 days.

7

NB! In the presence of/suspicion of secondary infection, local instillations are contraindicated: glucose solution, vitamin, enzyme, peptide preparations.

Surgical intervention: Laser methods: phototherapeutic keratectomy, crosslinking.

TREATMENT TACTICS AT INPATIENT LEVEL: relief of inflammation, complete resorption of infiltrate or with formation of opacity. Prevention of development of threat of perforation / corneal perforation.

patient observation card, patient routing (schemes, algorithms):

Scheme – Routing of patient with keratitis

KERATITIS outpatient treatment

superficial deep recovery recovery with formation of

opacity corneal ulcer / threat of perforation

inpatient treatment

outpatient observation

non-drug treatment • Regimen: III; • Diet: table No. 15.

LE – C

fluoroquinolone group eye drops 0.5% 5 ml conjunctival sac Antimicrobial drug Ofloxacin drops Instillations into

LE – B

fluoroquinolone group eye drops 0.5% 5 ml conjunctival sac M-Cholinolytics Tropicamide 0.5%, 1% Instillations M-cholinergic receptor blocker Phenylephrine Instillations into

in combination with alpha- hydrochloride 50 mg, conjunctival adrenomimetic tropicamide 8 mg sac (mydriatic) eye drops 5 ml M-Cholinolytic Atropine 1% eye Instillations into

LE - C

prolonged action, drops conjunctival mydriatic agent sac Instillations into Tear preparation Sodium hyaluronate conjunctival

sac Sodium hyaluronate Instillations into Keratoprotector 0.15%, dexpanthenol 2 conjunctival registered % sac in RK as MD Instillations into

Keratoprotector Dexpanthenol 5% gel conjunctival registered sac in RK as MD List of additional medications (less than 100% probability of use) Drug group international Method of administration Level of nonproprietary evidence name Antimicrobial bacteriostatic sulfanilamide Sulfacetamide drops agent, eye drops 20%, 30% 15

ml Instillations into conjunctival sac

Antimicrobial drug Ciprofloxacin 0.3% Instillations into fluoroquinolone group

ml

(LE - B)

sac Antimicrobial drug Tobramycin 5 ml aminoglycoside group Instillations into conjunctival sac antibiotic fluoroquinolone Ofloxacin eye ointment Instillations into conjunctival sac antiviral drug acyclovir tablets per os antiviral drug antiseptic acyclovir ointment chlorhexidine 0.02% Instillations into conjunctival sac Instillations into

(LE - C) (LE - C)

10 antiseptic eye drops conjunctival sac

antiseptic

antifungal drug

Antiallergic agent — H1-histamine receptor blocker Antiallergic agent — H1-histamine receptor blocker Regenerators and reparants

Beta-adrenoblockers non-selective

Alpha-adrenomimetic (Alpha-agonists)

Beta-adrenoblockers non-selective+ carbonic anhydrase inhibitors Diuretics Atropine 0.1% solution 1 ml

Local anesthetic agent

Fluconazole Ceftriaxone (vial for IV administration)

Dexamethasone 0.1% 10 ml

dexamethasone in combination with ofloxacin

dexamethasone in combination with ciprofloxacin

dexamethasone in combination with tobramycin

Dexamethasone 0.4% 1 ml

povidone-iodine betadine 1% eye drops

Fluconazole 0.2% Instillations into conjunctival sac Instillations into conjunctival sac Cetirizine 10 mg per os Chloropyramine 20 mg per os

Dexpanthenol

Timolol maleate 0.25%, 0.5%

Brimonidine

Timolol maleate+brinzolamide

Acetazolamide 250 mg M-cholinolytic prolonged action, mydriatic agent Proxymetacaine eye drops 15 ml

antifungal drug cephalosporin antibiotics

Corticosteroid for local application in ophthalmology Corticosteroid + antibiotic for local application in ophthalmology Corticosteroid + antibiotic for local application in ophthalmology Corticosteroid + antibiotic for local application in ophthalmology Corticosteroid

Instillations into conjunctival sac Instillations into conjunctival sac Instillations into conjunctival sac Instillations into conjunctival sac per os

subconjunctival injection

Instillations into conjunctival sac solution for intravenous administration solution for intramuscular injections Instillations into conjunctival sac Instillations into conjunctival sac

Instillations into conjunctival sac

Instillations into conjunctival sac

periocular injections

(LE - C) (LE – B) (LE – C) (LE – C) (LE – C) LE – B LE – B

LE – B LE-C (LE – C) LE-B (LE – B) (LE – B) (LE – B) LE-B

LE-B

LE-B (LE - B)

Glucocorticoids for Dexamethasone solution periocular injections LE-C 11 systemic use Glucocorticoids for local application in ophthalmology Vitamins and vitamin-like agents for injections 0.4% 1 ml Betamethasone dipropionate 5 mg

Riboflavin in crosslinking as consumable material Parabulbar injections

Instillations into conjunctival sac during crosslinking

LE – B registered in RK as MD

Surgical intervention (LE - B): Laser methods: phototherapeutic keratectomy, crosslinking.

Indicators of surgical treatment effectiveness: 1 severity and relief of corneal syndrome 2 corneal epithelialization 3 severity and relief of corneal edema 4 infiltrate resorption: depth, extent, edge character 5 visual acuity improvement 6 prevention of perforation

Further management: observation at polyclinic at place of residence: monitoring of corneal condition once a week – 1st month, once every 2 weeks – 2nd month, once a month – up to six months.

Indicators of treatment effectiveness: severity and relief of corneal syndrome corneal epithelialization

12

severity and resolution of corneal edema

resorption of infiltrate: depth, extent, character of the edge

formation of opacity

improvement (not always) / preservation of visual acuity

prevention of perforation

ORGANIZATIONAL ASPECTS OF THE PROTOCOL:

7.1 List of protocol developers with qualification data: 1. Isergepova Botagoz Iskakovna – Candidate of Medical Sciences, highest category physician, Senior Lecturer of the Postgraduate Education Department, JSC "Kazakh Research Institute of Eye Diseases", Almaty. 2. Zhakybekov Ruslan Adilovich – Candidate of Medical Sciences, highest category physician, Head of the Department of the branch of JSC "Kazakh Research Institute of Eye Diseases", Astana. 3. Izteleuova Aida Aibekovna – ophthalmologist of the 1st category, Consultative-Rehabilitation Department of JSC "Kazakh Research Institute of Eye Diseases", Almaty. 4. Sayat Malik – physician of the branch of JSC "Kazakh Research Institute of Eye Diseases", Astana. 5. Uldanov Oleg Galimovich – Associate Professor of the Department of Ophthalmology of RSE on REM "National Medical University", Almaty.

Conflict of interest: none.

Reviewers: Utelbayeva Zauresh Tursunovna – Professor of the Department of Ophthalmology of RSE on REM "National Medical University"

Indication of conditions for protocol revision: Revision of the protocol 5 years after its publication and from the date of its entry into force or in the presence of new methods with evidence level.

List of references used:

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Keay L, Edwards K, Naduvilath T, et al. Microbial keratitis predisposing factors and morbidity. Ophthalmology 2006;113:109-16.

Orlans HO, Hornby SJ, Bowler IC. In vitro antibiotic susceptibility patterns of bacterial keratitis isolates in Oxford, UK: a 10-year review. Eye (Lond) 2011;25:489-93.

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http://www.who.int/features/2015/essential_medicines_list/com 15

Indications for planned hospitalization:

• Ineffectiveness of outpatient treatment with development of complications - Negative treatment dynamics

Indications for emergency hospitalization:

• Ineffectiveness of outpatient treatment with development of complications - Negative treatment dynamics - Threat of corneal perforation / descemetocele