372FM.5 OPHTHALMIC

Contents Page Storage of Swabs and Media in , Stoke Mandeville Hospital ...... 1 1. ...... 1 a) Bacterial Conjunctivitis ...... 1 b) Viral Conjunctivitis ...... 2 c) Conjunctivitis ...... 3 2. (‘Ophthalmia Neonatorum’) ...... 4 3. ...... 5 4. Preseptal and ...... 5 a) Preseptal ...... 5 b) Orbital ...... 6 5. ...... 6 a) Bacterial Corneal Abscess (Keratitis) ...... 7 b) Keratitis ...... 8 c) ...... 8 d) ...... 9 e) Post-operative ...... 10 6. Management of Acute Endophthalmitis (post-operative endophthalmitis) ...... 10 Protocol for Obtaining Ocular Samples for Microscopy and Culture and Subsequent Intravitreal Injection in Presumed Bacterial Endophthalmitis...... 11 7. Endogenous Endophthalmitis ...... 13 a) Bacterial ...... 13 b) Fungal ...... 14 8. References ...... 15

Storage of Swabs and Media in Ophthalmology, Stoke Mandeville Hospital The following items are stored in the refrigerator in treatment room on ward 14 in the Mandeville building:  Bacterial culture media: Blood/chocolate  Fungal culture media: Sabouraud agar  Chlamydia/viral swabs with transport media  Microscope slides Ophthalmology staff are responsible for maintaining the stock of materials and ensuring these are in date. Bacterial culture plates should be inoculated (but not spread) by the ophthalmology clinician. If urgent microbiological sampling is required on a patient seen in Wycombe Ophthalmology Outpatients, the patient will need to be sent to the Ophthalmology Department at Stoke Mandeville Hospital where immediate plating of the specimen can take place.

1. Conjunctivitis a) Bacterial Conjunctivitis This is usually self-limiting (41% resolve within 6 - 10 days without antibiotic therapy) but antibiotic treatment speeds recovery. Conjunctival Swabbing  This need not be performed routinely for cases where the diagnosis is clear.  The exception to this is in the case of pregnant and lactating women (please see below).  If the patient has had severe symptoms for more than a week and has not responded to a first-line antibiotic, check and reinforce the frequency of instillation of treatment and consider taking conjunctival swabs for bacteria, viruses and chlamydia.  Fluorescein drops should not be instilled if it is intended to swab the eye.

Guideline 372FM.5 1 of 16 Uncontrolled if printed Treatment  First line: self-care.  Second line: 0.5% eye drops, 6 hourly (consider 2 hourly initially for more marked infections for the first 48 hours then reduce to 6 hourly). Chloramphenicol 1% eye ointment, applied every 6 - 8 hours, may be prescribed in place of drops.  Third line: If the patient is allergic to chloramphenicol or compliance with frequent instillation considered a likely issue, prescribe fusidic acid 1% eye drops 12 hourly (although this has a narrower spectrum of antibacterial activity).  Fourth line: If the patient does not respond to these agents, then a history regarding compliance should be sought, the diagnosis should be re-evaluated and swabs taken (see above). If the condition is still clinically deemed to be bacterial conjunctivitis 0.5% (preserved) eye drops every 2 hours for 48 hours then every 6 hours (unlicensed dose).  Preservative allergy: Chloramphenicol 1% eye ointment is the first line agent. If drops are required, use preservative-free drops, e.g. single-use, preservative free chloramphenicol 0.5%.  Therapy can be modified on receipt of bacteriology results.  Duration of treatment: Topical treatment should be continued for 48 hours after the symptoms have resolved, which usually means a course lasts 5 - 7 days. Management of Pregnant and Lactating Women  Swabbing should be performed from the outset so that treatment decisions are based on complete and relevant information.  As the condition is self-limiting, there is the option of not treating.  In and lactation the evidence suggests that fusidic acid 1% ointment 12 hourly is an appropriate choice. Cefuroxime 5% eye drops (preservative-free, unlicensed*) is an alternative. Advice to Patients Patients should be advised about general hygiene measures to avoid the spread of : Frequent , avoidance of sharing flannels and towels.

b) Viral Conjunctivitis Management and Treatment  If confirmation of viral diagnosis is required, a swab should be taken using the Chlamydia/viral specimen collection kit. Rub the conjunctival mucosa as hard as can be tolerated to obtain mucosal cells, then break off the swab in the transport media and send to the laboratory.  Symptomatic relief may be given with the use of ocular lubricants, e.g. carbomer 980 0.2% eye gel - 1 drop when required up to 6 hourly.  There is no evidence that the use of topical for the secondary prevention of bacterial conjunctivitis is beneficial. However, in severe cases, topical treatment can be given as per the bacterial conjunctivitis protocol.  For treatment of keratitis – see section 5.  Adenovirus/ Self-limiting with improvement of symptoms and signs within 5 - 14 days.  (HSV) – if keratitis, see section 5 - Usually subsides without treatment within 4 - 7 days unless complications occur. - Topical and/or oral antiviral treatment recommended for HSV conjunctivitis to prevent corneal infection. - First line: 3% ointment 5 times a day for 7 days (or continue for at least 3 days after complete healing) and/or aciclovir 400 mg PO 5 times a day for 5 days. - Second line: Ganciclovir 0.15% eye gel 5 times a day. Guideline 372FM.5 2 of 16 Uncontrolled if printed  Varicella (Herpes) Zoster Virus (VZV) - immunocompetent - affecting the ophthalmic branch of the trigeminal nerve; typical unilateral dermatomal pain, virtually always followed by a rash. Severe ocular complications can occur but are rare. Mild conjunctival involvement is common. - Seek an ophthalmological opinion within the first three weeks (as ocular may occur late). - Give early treatment with oral aciclovir 800 mg five times daily for 7 days to reduce the long term ocular complication rate. - Do not use topical steroids without ophthalmological guidance. - If the is more severely involved, the looks hazy or the patient complains of decreased vision, an ophthalmological opinion is required (urgency dependent on severity). Infection Control  Adenoviral/enteroviral conjunctivitis is extremely contagious. Avoid sharing personal items, use meticulous hand washing and avoid close personal contact for approximately two weeks.  For patients with adenoviral conjunctivitis, dispose of unclean contact lenses.  The (including the on-off switch) must be cleaned thoroughly with alcohol swabs after examination of the patient. Usual hand hygiene guidance applies.

c) Chlamydia Conjunctivitis This typically affects sexually active young adults. The eye lesions usually present about one week following sexual exposure and may be associated with a non-specific or cervicitis. Symptoms Patients almost invariably have bilateral involvement with a mucopurulent discharge, redness and discomfort but presentation with a unilateral can also occur. Signs Large opalescent follicles are found in the conjunctival fornices. Follicles can also occur at the limbus and on the bulbar conjunctiva as the disease develops. Pre-auricular lymphadenopathy is common, but associated fever and pharyngitis is absent. An epithelial keratitis is common; marginal infiltrates and a superior micropannus can occur. Investigation A swab should be taken using the Chlamydia/viral specimen kit. Rub the conjunctival mucosa as hard as can be tolerated to obtain mucosal cells, then break off the swab in the transport media and send to the laboratory. Management This must be given and should be prescribed in eye casualty when the diagnosis is confirmed (and considered prior to confirmation if the diagnosis is strongly suspected). Discussion with the genitourinary medicine (GUM) department regarding the timing of systemic swabs should be undertaken. Adult patients should be referred to a local GUM clinic where they will be screened for other sexually transmitted infections and undergo sexual partner tracing.  First line: Doxycycline PO 100 mg 12 hourly for 7 days (contraindicated in pregnancy)  Second line: Azithromycin PO 1 g stat (including pregnancy, unlicensed* use).  In pregnancy (alternative to azithromycin): PO 500 mg 6 hourly for 7 days or 500 mg 12 hourly for 14 days is the second line agent of choice.  For treatment of Chlamydial infection in children see section 2, Neonatal Conjunctivitis.

Guideline 372FM.5 3 of 16 Uncontrolled if printed 2. Neonatal Conjunctivitis (‘Ophthalmia Neonatorum’) Neonatal conjunctivitis is one type of conjunctival infection occurring during the first month of life. It is a notifiable disease and significant conjunctivitis should be referred urgently to an ophthalmologist. Causes These include bacteria and Chlamydia, and more rarely Herpes simplex virus and chemical irritants. Almost any common bacterial pathogen can cause the condition, but amongst bacterial causes infection is of particular concern as it can cause corneal ulceration of very rapid onset. Investigations  Take a bacterial swab and a separate swab for Chlamydia (see section 1C).  Take a viral swab, if clinically indicated.  If clinically indicated, do a conjunctival scrape and send for urgent Gram stain (discuss with microbiologist first), looking particularly for Gram negative diplococci.  Try to view the to exclude opacity (corneal infection) or other abnormality (enlarged corneas may indicate congenital ; sometimes presents as conjunctivitis). Treatment  The opinion of a paediatrician should be sought in most cases, but particularly if the child is systemically unwell or if Chlamydia is suspected. Mild bacterial conjunctivitis – a slightly sticky eye in a well child – can generally be managed without paediatric input.  Once swab results are obtained, treat according to the diagnosis. Chlamydial conjunctivitis (suspected/confirmed)  The incubation period is 5 - 14 days.  Initially unilateral, it usually becomes bilateral.  The lids are swollen and there is a watery, mucopurulent discharge. The conjunctival reaction is papillary rather than follicular.  It can give rise to conjunctival scarring, superior corneal pannus and opacity.  Systemic complications include rhinitis, otitis and pneumonitis.  Treatment: Erythromycin 12.5 mg/kg PO 6 hourly for 2 weeks (extend to 3 weeks if pneumonitis evident).  Refer to GUM clinic if Chlamydia infection is confirmed, as mother will require further investigations and treatment. Gonococcal conjunctivitis  Usually occurs in the first few days of life.  Rapidly progressing and severe purulent conjunctivitis.  The cornea can be rapidly affected; ulceration and even perforation can occur.  If microscopy shows Gram negative diplococci, consistent with Neisseria gonorrhoeae, treat infection with cefotaxime 100 mg/kg (max. 1 g) IM stat dose.  At the discretion of the consultant ophthalmologist and paediatric team also consider administering ceftazidime 5% eye drops (preservative free, unlicensed*) six times a day until resolved.  Refer to GUM clinic if gonorrhoeal infection is confirmed, as mother will require further investigations and treatment. Conjunctivitis caused by other bacteria  Typically, symptoms develop in the first 4 - 5 days of life, but they can occur at any time.  Organisms include: , Staph. epidermidis, pneumoniae, , Serratia spp., Pseudomonas spp. and Haemophilus spp.  Treatment: Chloramphenicol 0.5% eye drops 6 hourly for 7 - 10 days, commenced after appropriate swabs have been taken. Guideline 372FM.5 4 of 16 Uncontrolled if printed Herpes simplex  Blepharoconjunctivitis usually develops in the first 5 - 7 days of life; keratitis can occur.  Treatment: topical aciclovir 3% applied 5 times daily for at least 3 days after complete healing but the regimen will be guided by ophthalmology specialist.

3. Blepharitis  Warm compresses, hygiene with baby shampoo, lid massage, tear supplements and topical anti-inflammatory agents may be used to alleviate symptoms. Avoid cosmetics.  Topical antibiotics should usually be reserved for second-line use when eyelid hygiene measures are ineffective after 2 weeks.  Topical antibiotics should be applied after eyelid hygiene and/or at night before sleep. The frequency of application depends on the severity of the blepharitis and its response to treatment.  If there are clear signs of anterior blepharitis or meibomian gland dysfunction, consider oral antibiotics. Anterior blepharitis or meibomian gland First Line dysfunction Self-care If unresponsive after 2 weeks, Chloramphenicol 1% Doxycycline 100 mg 24 hourly for 4 weeks ointment apply 12 hourly for 6 weeks then 50 mg 24 hourly for 8 weeks

4. Preseptal and Orbital Cellulitis Both preseptal and orbital cellulitis occur most commonly in children. Preseptal cellulitis is localised anterior to the orbital septum, e.g. outside the bony , whereas orbital cellulitis involves infection of fat and muscle within the bony orbit. The two conditions may be difficult to differentiate with early radiological imaging (computerised tomography (CT) scan) sometimes required. a) Preseptal Clinical features More common than orbital cellulitis. Usually arises from a contiguous infection of the soft tissues of the face/ secondary to local trauma, foreign bodies, insect or animal bites. The patient presents with swelling and erythema of the tissues surrounding the orbit. Fever may also be present. The most common pathogens include , Staphylococcus aureus, other streptococcal species and anaerobes. Diagnosis This is based on clinical examination and history, e.g. insect bite, local trauma, etc. Severe preseptal cellulitis is often difficult to distinguish from orbital cellulitis and may require a CT or magnetic resonance imaging (MRI) scan to establish the diagnosis. Treatment Some cases may be managed as an outpatient with oral antibiotics and daily follow-up. If the patient fails to improve within 24 hours or is thought to have a more severe infection, admission for IV antibiotics and further evaluation will be necessary. First Line Alternative OR Allergy See BNFc for paediatric doses. See BNFc for paediatric doses. Co-amoxiclav 1.2 g IV 8 hourly then Children with non-severe penicillin allergy: IV. switch to co-amoxiclav 625 mg PO Adult: 8 hourly when clinically appropriate. <80 years: Clindamycin 300 mg PO 6 hourly (600 – 900 mg IV 6 hourly if nil by mouth (NBM)). >80 years: Clarithromycin 500 mg PO (IV if NBM) 12 hourly plus metronidazole 400 mg PO (or 500 mg IV if NBM) 8 hourly. Total duration: 7 days

Guideline 372FM.5 5 of 16 Uncontrolled if printed b) Orbital Clinical features This is a serious condition, as complications lead to mortality in 1 - 2% and visual loss in 3 - 11% cases. Acute sinusitis is the most common predisposing factor but orbital cellulitis can also result from ophthalmic surgery, orbital trauma and dental, middle ear or facial infection. The most common pathogens include Streptococci spp., Staphylococcus aureus and anaerobes. Orbital cellulitis should be suspected if any of the following signs are present:  Proptosis  displacement  Limitation of eye movement  Double vision  Chemosed conjunctiva  Visual loss Complications include the development of localised abscesses or extra-orbital extension causing visual loss, intracranial abscess, or septic cavernous sinus thrombosis. Diagnosis This is based on the history, physical examination, including visual acuity and ocular motility assessment and radiological studies (either CT or MRI scan usually). Treatment Parenteral broad-spectrum therapy is always required initially for orbital cellulitis. First Line Alternative OR Penicillin Allergy Children: Children: Ceftriaxone* IV plus clindamycin PO * IV plus IV plus See BNFc for paediatric doses. metronidazole IV

See BNFc for paediatric doses.

Adults: Adults: Ceftriaxone* 2 g 12 hourly IV plus Vancomycin* IV (see Guideline 241 Intravenous metronidazole* 500 mg 8 hourly IV then Vancomycin for Adults) plus ciprofloxacin 400 switch to co-amoxiclav 625 mg PO 8 hourly mg IV 12 hourly plus metronidazole* 500 mg IV when clinically appropriate. 8 hourly.

Fluoroquinolone Patient Safety Information Duration: 3 days IV then review with ENT and microbiology, consider IV to oral switch depending on clinical progress. Total duration: 7 - 10 days. * unlicensed indication The patient should be kept on 4 hourly neuro/ophthalmic observations at the beginning of treatment. Check for any evidence of compromise on the same side and on the other side (suggesting possible cavernous sinus thrombosis). If there is no clinical improvement after 36 - 48 hours or a swinging pyrexia persists, consider repeating the radiological scan. If any abscess has developed this will need emergency surgical drainage. All orbital cellulitis treatment should be in consultation with ENT and microbiology.

5. Keratitis  All patients with a and stromal suppuration should be presumed to have microbial keratitis.  Do not use chloramphenicol for empiric treatment of keratitis in cosmetic contact wearers due to the likelihood of a Pseudomonas infection. Specimens for Investigation All patients with suspected microbial keratitis should have a corneal scrape sent for microbiological analysis. This should include fungal and viral investigations (Herpes simplex) and polymerase (PCR) for acanthamoeba if clinically indicated (see section 5c). Guideline 372FM.5 6 of 16 Uncontrolled if printed Consider Admission to Hospital Most patients with severe microbial keratitis need admission to hospital for intensive antimicrobial treatment. Some mild cases can be managed as an outpatient. The decision on whether to admit or not must be left to clinical judgment of the managing senior ophthalmologist. Prescribing should be done in hospital as many of the products are unlicensed and difficult to obtain in the community. Topical steroids  Before initiating topical steroids, the case must be discussed with a senior member of the ophthalmic team.  If there is significant ocular inflammation, steroids should be considered after the first 48 hours following discussion of the culture results with microbiology.  Steroids can be used as part of the management of bacterial keratitis but not fungal or acanthamoeba infection.  Corticosteroids will not shorten the natural course of the disease but will merely suppress the corneal inflammation and cessation of treatment may be associated with a rebound exacerbation.  Treatment should therefore be reserved for those with a stage 2 or 3 keratitis (focal white subepithelial opacities and anterior stromal infiltrates).  Prednisolone 0.5% or fluorometholone 0.1% eye drops can be prescribed. The frequency of drop instillation should be according to the clinical picture, usually on a twice daily to four times daily basis, with gradual tapering. Failure to improve If the signs are not improving despite apparent use of the correct topical medication, microbiology should be consulted. Consideration should be given to stopping the medication for 24 hours and re-scraping the cornea. a) Bacterial Corneal Abscess (Keratitis) Cases of suspected bacterial keratitis should be managed by an ophthalmologist. Treatment: Mild (bacterial) keratitis Severe (bacterial) keratitis Not requiring hospital admission Requiring hospital admission 0.3% (preserved) eye drops Moxifloxacin 0.5% eye drops every hour day and night hourly, reviewed after 48 hours and (unlicensed dose) for 48 hours (prescribed on the treatment adjusted according to clinical inpatient chart as soon as relevant specimens have response. been taken) After 48 hours, frequency of treatment may be reduced Fluoroquinolone Patient Safety Information to 2 hourly while awake for a further three days.

Lesions that potentially extend into the anterior chamber or into the : Moxifloxacin 400 mg PO 24 hourly for 10 days (unlicensed indication).

NB Contraindicated in severe liver disease. Patients should be counselled to monitor for signs of liver dysfunction. Fluoroquinolone Patient Safety Information Ongoing management should then be adjusted according to clinical response and according to the results of microbiological investigations. The following antibiotics can be used to modify treatment according to sensitivity results, taper frequency according to severity and continue until resolution: G Gentamicin 1.5% (preservative free, unlicensed*) G Ceftazidime 5% (preservative free, unlicensed*) G Vancomycin 5% (preservative free, unlicensed*)

Allergies If there are known antibiotic allergies which preclude the use of these treatments, then discuss alternative medications with microbiology and/or pharmacy. Guideline 372FM.5 7 of 16 Uncontrolled if printed b)  Acute with a watery discharge and variably decreased vision. Corneal involvement may be macroscopically evident, particularly with fluorescein staining (may be a classic ‘dendritic’ ulcer).  Contact ophthalmologists for advice on investigation and treatment.  Beware the differential diagnosis of a red eye with a hazy cornea - acute glaucoma, severe iritis, corneal ulcer. First Line Alternative Epithelial, geographic, stromal or necrotising: Epithelial, geographic, stromal or Aciclovir 3% eye ointment 5 times daily for 7 days, necrotising: then 8 hourly for 7 days then taper as required Trifluorothymidine 1% (unlicensed*) one drop 5 Or times day for 7 days then 8 hourly for 7 days Ganciclovir 0.15% eye gel (preserved) one drop 5 times daily for 7 days then 8 hourly for 7 days For prophylaxis of stromal keratitis, endotheliitis and keratouveitis: Aciclovir 400 mg PO 12 hourly under specialist supervision

c) Acanthamoeba Keratitis Clinical features Acanthamoeba keratitis occurs predominantly in patients who are wearers. It usually presents with a unilateral red eye; marked pain is a common feature and this may be disproportionate to the clinical signs. Features typical of Acanthamoeba keratitis are persistent epithelial defects, subepithelial or elevated infiltrates, as well as a ‘classic ring’ pattern of stromal infiltration, which is seen as the keratitis progresses. Radial linear (peri- neural) infiltrates indicate nerve involvement and are also typical of the condition. Investigation If acanthamoeba is suspected send a corneal scrape in PCR transport medium, and inform the microbiology lab of the sample whether in hours or out of hours. If available, the contact lens fluid container and the contact lens should also be sent to the laboratory for examination. Microscopy of spun contact lens solution may allow immediate detection of trophozoites and cysts. A corneal epithelial biopsy should also be sent in normal to microbiology where a portion can be separated and sent for histology as necessary. Before commencing treatment all cases of Acanthamoeba keratitis should be discussed with the on-call consultant ophthalmologist. Treatment: First Line Alternative Treat hourly day and night for 48 hours then hourly by day for 72 hours then every 2 hours for 3 - 4 weeks then tailored to each individual case. Polihexanide (polyhexamethylene ) If unresponsive to both combinations of 1st line (PHMB) 0.02% eye drops, preservative free, therapy, consider (unlicensed*) gluconate 0.2% eye drops plus preservative-free (unlicensed*) isetionate 0.1% eye drops, Take care to select the correct strength! preserved (unlicensed for this indication*)

Alternatively Chlorhexidine gluconate 0.02% eye drops, preservative-free (unlicensed*) Take care to select the correct strength! plus Propamidine isetionate 0.1% eye drops, preserved (unlicensed for this indication*) Guideline 372FM.5 8 of 16 Uncontrolled if printed d) Fungal Keratitis Cases of suspected fungal keratitis should be managed by an ophthalmologist. Diagnosis Can be challenging and may be delayed, it can be made on clinical, microbiological or imaging grounds which may include:  An appearance suggestive of infection of the cornea9  Direct imaging by confocal microscopy  Positive culture  Histological evidence from smear samples or tissue from a corneal biopsy.  18S PCR Risk factors  Contact lens wear  Topical steroid use  Corneal surgery  Chronic ocular surface disease  Trauma  Travel to tropical regions Treatment Stop any topical steroid, if patients are on this at presentation, as their use will exacerbate a fungal infection. Empirical Treatment Continuation Lesions confined to the superficial layers of the cornea are initially treated empirically with topical therapy. G 5% (preserved) (unlicensed*), apply hourly Once culture sensitivities are known, day and night for 48 hours, then reduce frequency to change treatment if necessary and follow hourly daytime only. Once epithelial ulceration shows guidance from microbiology. signs of healing the frequency can be gradually reduced. Yeast (Candida) If infection is severe G Chlorhexidine 0.2% (preservative G Amphotericin 0.15% (preservative free) free) (unlicensed*) may be added. (unlicensed*) especially for C. albicans Take care to select the correct strength! Or alternatively, G Voriconazole 1% (preserved or preservative free) (unlicensed*)

Filamentary G Natamycin 5% (preserved) (unlicensed*) Treatment courses need to be long continuing 6 hourly for at least 4 weeks

Empirical Treatment Alternative Lesions that potentially extend into the anterior chamber or into the sclera, in addition to intensive topical treatment above may require: Oral therapy: (achieves good intraocular levels and Itraconazole 100 - 200 mg PO 12 hourly intravenous administration is not necessary unless the oral Intracameral (anterior chamber) route cannot be given/tolerated). amphotericin Dose 5 micrograms in 0.1 ml. Voriconazole: Initial loading dose 400 mg 12 hourly (patients >40 kg) or 200 mg 12 hourly (patients <40 kg) for 1 day, then Maintenance dose 200 mg 12 hourly (patients >40 kg) or 100 mg 12 hourly (patients <40 kg) for 13 days If appropriate treatment may be continued for longer time with microbiology approval. Intracameral (anterior chamber) Voriconazole: Dose 50 - 100 micrograms in 0.1 ml (see Medusa for details on preparation of product). Intrastromal voriconazole: Dose 50 micrograms in 0.1 ml. Guideline 372FM.5 9 of 16 Uncontrolled if printed Voriconazole Monitoring  Test liver function before starting treatment with voriconazole and at least weekly during the first month of treatment.  Advise patients to avoid sunlight exposure while taking voriconazole.  Voriconazole has a narrow therapeutic window. Due to inter-individual variability of voriconazole metabolism, therapeutic drug monitoring is recommended. Send clotted blood to Serology Laboratory, SMH, taken just before one of the doses on day 5 - 7 of therapy. Serum will be sent to Antimicrobial Reference Laboratory, Bristol, with result available the following day. Pre-dose level of 1.0 - 4.5 mg/l is satisfactory; consider repeating in one week.

e) Post-operative Endophthalmitis Prevention Risk factors It is essential to identify blepharitis, nasolacrimal obstruction or severe atopic disease at the time of listing the patient for surgery and ensure that this is managed appropriately. The pre- operative assessment can be used to check that management of any such conditions is optimal. A date for surgery should not be set until these conditions have been managed. Preparation of operative field  Practice meticulous, sterile periocular/ocular preparation regimen before surgery: Povidone 5% is recommended for routine eyelid and skin pre-operative preparation. (The 5% aqueous solution, a 1:1 dilution of the 10% solution with sterile water (unlicensed*) is efficacious and causes little epithelial toxicity). A minimum skin contact time of one minute is advised. The only contraindication is known iodine allergy.  A drop of 5% povidone iodine (unlicensed*) should be instilled at the time the anaesthetic is given.  It is important that the lashes are isolated from the operative field by the plastic drape. Proper drying of the lids after toilet is helpful. If the lashes are not adequately isolated consider re-draping. Post-operative antimicrobial prophylaxis First Line Type 1 penicillin hypersensitivity Intracameral cefuroxime 1 mg plus subconjunctival Subconjunctival gentamicin 20 mg (unlicensed*) betamethasone 2 mg (unlicensed*) or plus betamethasone 2 mg (unlicensed*) or 2 mg (unlicensed*). dexamethasone 2 mg (unlicensed*).

Post-operative eye drops for a minimum of two weeks for intraocular surgery. Options include:  Dexamethasone 0.1% eye drops one drop 6 hourly plus chloramphenicol 0.5% eye drops one drop 6 hourly. Add ketorolac 0.5% eye drops one drop 8 hourly for other selected risk groups, including diabetic patients.  Maxitrol® eye drops 6 hourly.  Maxitrol® eye ointment 12 hourly (if patient unable to instill drops). Clear instructions should be given to each patient regarding the normal post-operative course.

6. Management of Acute Endophthalmitis (post-operative endophthalmitis) Maintain a high index of suspicion and a low threshold for action. If in doubt, admit and investigate/treat as appropriate following urgent discussion with a consultant ophthalmologist. The opinion of a vitreoretinal surgeon should be obtained if clinically indicated; early vitrectomy should be considered if the visual acuity is worse than ”perception of light” on presentation, and in patients who present early after surgery with overwhelming inflammation and rapidly declining vision.

Guideline 372FM.5 10 of 16 Uncontrolled if printed 1. Full initial (at least daily thereafter) ophthalmic examination with careful documentation of:  Visual acuities  Presence or absence of a relative afferent pupillary defect  Anterior chamber activity  Vitreous activity 2. If there is no posterior segment view consider serial ultrasound to document the state of the posterior segment before diagnostic sampling. 3. Obtain informed consent before sampling emphasising that:  This is a potentially serious situation which could result in visual loss.  Therapy will proceed according to best clinical practice as documented in the current literature. 4. The aqueous and vitreous should be sampled under a local or general anaesthetic as necessary, prior to the initiation of antibiotic therapy. 5. Take samples for Gram stain, culture and sensitivity after liaising with the microbiology department (inform the on-call biomedical scientist if out of hours). A minimum sample of 0.2 ml is desirable.

Protocol for Obtaining Ocular Samples for Microscopy and Culture and Subsequent Intravitreal Antibiotic Injection in Presumed Bacterial Endophthalmitis. Pre-theatre 1. To exclude , if there is no view of the posterior segment the patient should undergo a B-scan ultrasound. 2. An endophthalmitis kit/box should be available in every eye unit. This will contain all equipment needed for intraocular sampling and administration of intravitreal antibiotics. 3. Consider performing the intravitreal procedure under local anaesthesia if a substantial delay is likely before general anaesthesia is available. In theatre 1. Administer topical anaesthetic G Oxybuprocaine hydrochloride 0.4%. Sub-Tenon’s anaesthetic (lidocaine 2% +/- bupivacaine 0.5%) may be administered as desired. 2. Perform a vitreous tap using a 25 g needle. A minimum sample of 0.2 ml is desirable. If no sample is forthcoming, partially withdraw the needle and then re-insert in a slightly different direction. If still unsuccessful, retry with a 23 g needle. An AC tap is desirable but not mandatory. Take samples for Gram stain, Giemsa stain, culture and sensitivity. Inform the pathology/microbiology department (or the on-call biomedical scientist, if out of hours) the sample analysis has to be done urgently.

Guideline 372FM.5 11 of 16 Uncontrolled if printed 3. Administer intravitreal antibiotics: First Line Type 1 penicillin hypersensitivity Vancomycin (active against Gram positive Vancomycin (active against Gram positive organisms) 2 mg in 0.1 ml (unlicensed*) and organisms) 2 mg in 0.1 ml (unlicensed*) and ceftazidime (broad spectrum activity, including amikacin (active against Gram negative organisms, Pseudomonas) 2 mg in 0.1 ml (unlicensed*) including Pseudomonas) 0.4 mg in 0.1 ml (unlicensed*).

Amikacin carries a higher risk of retinal infarction, use only if well-defined penicillin or cephalosporin allergy. The dose of these antibiotics is critical; mistakes can result in irreversible damage to the . If pre-prepared preparations are not available, the antibiotics should be prepared, observing sterile precautions. The drugs should not be mixed in the same syringe, and should be injected separately into the eye. Avoid solutions or preparations containing preservatives. The quantities for intravitreal injection may be drawn up in 1 ml syringes, for a dose of 0.1 ml, and injected with a 25 or 27 gauge needle. Make sure to fill the dead space with antibiotic solution.

Intravitreal injections will need to be prepared in ophthalmic theatre immediately prior to use as outlined in the Injectable Medicines Guide (Medusa).

Dose: 2 mg in 0.1 ml. Vancomycin (active against Gram positive organisms) (unlicensed*) Only sodium chloride 0.9%, not water for injection (WFI), should be used with vancomycin for the final dilution. a) Reconstitute a 500 mg vial with 8 ml of sodium chloride 0.9%. b) Withdraw entire contents and make up to 10 ml with sodium chloride 0.9% mix thoroughly - this gives a concentration of 50 mg/ml. c) Inject 2 ml back into the vial and add 3 ml of sodium chloride 0.9% to give a concentration of 20 mg/ml. d) Draw up about 0.2 ml (excess to facilitate priming) into a 1 ml syringe. When ready to inject, fit the Rycroft cannula or the needle to be used and discard all but 0.1 ml (contains 2 mg of antibiotic) for injection. Dose: 2 mg in 0.1 ml. 4. Sub-Tenon’s betamethasone 2 mg (unlicensed*) should be administered following the intravitreal antibiotic. 5. Post-operative management i. Topical treatment Chloramphenicol 0.5% single use, preservative-free eye drops 6 hourly plus 1% single use, preservative-free eye drops 12 hourly plus Dexamethasone 0.1% single use, preservative-free eye drops 2 hourly Duration dependent on individual patient response, usually 5 - 10 days ii. Oral treatment  Moxifloxacin 400 mg PO once daily to start on day 1 for 10 days. (Ciprofloxacin may be used if moxifloxacin is contraindicated.) Fluoroquinolone Patient Safety Information  Prednisolone 1 mg/kg (max. 80 mg) PO to start 24 hours after the intravitreal antibiotics (depending on response).  Lansoprazole 30 mg PO 24 hourly or ranitidine 150 mg PO 12 hourly for the duration of the prednisolone prescription.  Arrange for baseline bloods, blood glucose, blood pressure and weight. Inpatient care is preferable due to frequent monitoring and possible changes to treatment.  If the inflammatory signs (, red reflex, etc.) have not improved or have progressed after 48 hours, consider repeating the intravitreal antibiotics. If still no improvement, consider vitrectomy. Guideline 372FM.5 12 of 16 Uncontrolled if printed

7. Endogenous Endophthalmitis  Endogenous endophthalmitis is a rare condition in which there is blood-borne spread from an extraocular site to the eye.  It is potentially both life-threatening and sight-threatening.  The best outcome is associated with early diagnosis, so a high index of suspicion must be maintained for this condition.  Any case of suspected endogenous endophthalmitis should be discussed urgently with a consultant ophthalmologist.  An accurate ocular and systemic history is essential.  Underlying risk factors must be investigated (e.g. diabetes mellitus).  The source of infection must be sought.  Management must be in conjunction with physicians.  Systemic antimicrobial therapy is essential.  The administration of intravitreal antibiotics and the use of vitrectomy depend upon the severity of ocular involvement.  Eye involvement is bilateral in 25% of cases.  Close involvement with the microbiology department is mandatory.

a) Bacterial This almost always occurs in the context of a clinically unwell patient. Medical risk factors for bacterial endogenous endophthalmitis include diabetes mellitus, endocarditis, gastrointestinal disorders, malignancies and renal failure. Organisms:  Any bacterium could potentially give rise to this condition.  Gram positive are commonest (approximately 70%), of which streptococcal species (group B streptococci and Streptococcus pneumoniae especially) are most frequent. Staphylococcus aureus, Clostridium spp and Bacillus cereus can also occur.  Gram negative organisms include Escherichia coli (commonest), , , , . Sites of infection:  Any extraocular site could harbour the primary infection.  Commonest sources of infection are: Endocarditis, kidneys and urinary tract, gastrointestinal abscess, liver abscess, cellulitis, meningitis, indwelling catheters and fistulae, pneumonia. Investigation of causative organism and site of infection  This must be carried out in conjunction with physicians.  Cultures: Blood (two) and urine mandatory +/- anterior chamber and vitreous tap +/- lumbar puncture for cerebrospinal fluid any other specimen relating to the underlying cause  Other investigations to consider: Echocardiogram, endoscopy, chest X-ray and other radiological investigations where indicated, e.g. renal ultrasound.

Guideline 372FM.5 13 of 16 Uncontrolled if printed Treatment: Systemic and topical antibiotics should both be used. Treatment should be tailored to the underlying cause. I. Systemic antibiotics:  These are mandatory and should be continued for up to 3 weeks.  Before definite culture results are available, the initial antimicrobial therapy must be broad spectrum: Moxifloxacin 400 mg daily PO, may be altered according to systemic indication. Fluoroquinolone Patient Safety Information  Once cultures and sensitivities are known, treatment may be modified in conjunction with the microbiologists. II. Intravitreal antibiotics:  These are not always used in the management of endogenous endophthalmitis.  If used, the procedure and antibiotics are as outlined in Post-operative Endophthalmitis. III. Vitrectomy:  This is also controversial, but may be associated with a better visual outcome. The decision to proceed should be made on the basis of the patient’s general health and the degree of vitreous involvement. IV. Oral steroids:  This should only be considered once the infection (both systemic and ocular) is deemed to be under control and after liaison with physicians. Use prednisolone 1 mg/kg/day (max. 80 mg) PO in conjunction with a proton pump inhibitor, e.g. lansoprazole 30 mg PO 24 hourly. Further management depends upon the clinical response.

b) Fungal The causative agent is almost always Candida albicans. Patients fall into two main groups: i. Intravenous drug users who inject the organism along with contaminated lemon juice/drug. ii. Medically clinically unwell patients, often on ICU, via an indwelling catheter or line. Infections from Aspergillus species may occur occasionally. The underlying cause is usually intravenous drug abuse, immunosuppression, endocarditis or pneumonia. Management: I. Intravenous drug users:  Anterior chamber, vitreous tap and blood cultures can be taken for culture and sensitivities.  A pars plana vitrectomy should be considered where there is a heavy vitritis.  Systemic treatment must be given: Oral fluconazole 400 mg daily for a minimum of four weeks is recommended, subsequently proceeding according to the clinical response. If additional or alternative therapy is indicated, contact the microbiology department. II. Medically clinically unwell patients:  Take anterior chamber, vitreous tap and blood cultures for culture and sensitivities.  Systemic antifungals are necessary. First line: Fluconazole 400 – 800 mg IV/PO. Second line: Intravenous liposomal amphotericin (AmBisome®), 1 mg test dose followed by 3 mg/kg (rounded to the nearest 50 mg). This should be given in liaison with physicians and microbiologists. Length of treatment will vary on an individual patient basis. Intravitreal amphotericin (Fungizone®) 5 micrograms in 0.1ml (unlicensed*) or intravitreal voriconazole 50 micrograms in 0.1ml (unlicensed*) may be given. Intravitreal antifungals should be prepared in ophthalmic theatre immediately prior to injection as outlined in the Injectable Medicines Guide (Medusa).  A pars plana vitrectomy should be considered where there is a heavy vitritis.

Guideline 372FM.5 14 of 16 Uncontrolled if printed *Unlicensed Medicines (for further information see BHT Pol 071 (Annexe 4) Unlicensed Medicines Policy). The unlicensed eye drops in this guideline are categorised with the following risk: Drug Risk Medium – if purchased from Western G Ceftazidime 5% Royal Infirmary High - if made in Pharmacy Aseptics unit Medium – if purchased from Newcastle G Cefuroxime 5% NHS Trust High - if made in Pharmacy Aseptics unit G Chlorhexidine 0.02% Low G Chlorhexidine 0.2% Medium G Gentamicin 1.5% Low G Natamycin 5% Low G Polyhexanide (PHMB) 0.02% Low G Trifluorothymidine 1% Low G Vancomycin 5% Medium G Voriconazole 1% Medium Intravitreal antibiotics are all classified as HIGH risk if made in Pharmacy Aseptics unit or prepared in theatre.

The management of the three risk categories is summarised below: Risk Record Record Awareness of Verbal patient Written Record of Generic keeping keeping UMP status consent patient UMP status patient of of amongst documented consent on drug information receipt supply prescribers, in clinical documented chart, TTO, leaflet (PIL) pharmacists notes in clinical outpatient and nurses notes prescription Low   x x x x x Medium     x   High       

8. References 1. British National Formulary (BNF). 2. Electronic Medicines Compendium (www.medicines.org.uk/emc). 3. Moorfields Eye Hospital NHS Foundation Trust. Microguide App, Version 3.2, accessed 13th August 2018. 4. ESCRS Guidelines on Prevention, Investigation and Management of Post-operative Endophthalmitis, August 2007: European Society of and Refractive Surgeons. 5. 2015 UK national guideline for the management of infection with The British Association for Sexual Health and HIV (BASHH) - (https://www.bashhguidelines.org/media/1045/chlamydia-2015.pdf, accessed 13th August 2018). 6. Moorfields Eye Hospital Medicines Information Department. 7. Moorfields Pharmaceuticals Medicines Information Department. 8. Health Improvement Scotland, SIGN 104, Antibiotic prophylaxis in surgery, April 2014. 9. Thomas PA, Leck AK, Myatt M. Characteristic clinical features as an aid to the diagnosis of suppurative keratitis caused by filamentous fungi. Br J Ophthalmol 2005;89(12):1554-8. 10. UK Teratology Information Service. Use of Eye Drops in Pregnancy. Date of issue: April 2011, Version 1. Accessed 13th August 2018. 11. Public Health England, Management of Infection Guidance for Primary Care 2018/19, October 2017. Guideline 372FM.5 15 of 16 Uncontrolled if printed 12. Kalaiselvi.G., Narayana, S., Krishnan,T., Sengupta,S. Intrastromal voriconazole for deep recalcitrant fungal keratitis: a case series. Br J Ophthalmol. 2015 Feb; 99(2):195-8. https://www.ncbi.nlm.nih.gov/pubmed/25185253 accessed 19th September 2018. 13. Yajie, S., Zhuo, S., Yukai, C., Guohua, D. Corneal Debridement Combined with Intrastromal Voriconazole for Recalcitrant Fungal Keratitis, Journal of Ophthalmology, Volume 2018, Article ID 1875627, 8 pages, https://www.hindawi.com/journals/joph/2018/1875627/ accessed 19th September 2018. 14. Prakash, G., Sharma N., Goel, M., Titiyal, J.S., Vajpayee, R.B. Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis. Am J Ophthalmol. 2008 Jul;146(1):56-59. doi: 10.1016/j.ajo.2008.02.023. Epub 2008 Apr 24. https://www.ncbi.nlm.nih.gov/pubmed/18436173, accessed 19th September 2018. 15. Muthiah Srinivasan, M.D. et al. The Steroids for Corneal Ulcers Trial. Arch Ophthalmol. 2012 Feb; 130(2): 10.1001/archophthalmol.2011.303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830555/ , accessed 19th September 2018.

See also: BHT Pol 071 Annexe 4 - Unlicensed Medicines Policy* Guideline 6 Consent to Examination or Treatment Policy* Guideline 222 Adult and Paediatrics Injectables Guide* Guideline 241 Intravenous Vancomycin for Adults* *BHT users only

Title of Guideline Ophthalmic Infections Guideline Number 372FM Version 5 Effective Date July 2019 Review Date July 2022 Approvals: Antimicrobial Stewardship 20th November 2018 Committee Paediatric Information and 9th May 2019 Guidelines Group Paediatric Governance Dr Salgia - Chair’s Action 17th July 2019 Clinical Guidelines Subgroup 21st May 2019 Author/s Ophthalmology Consultants, Microbiology Consultants, Antimicrobial Pharmacist SDU(s)/Department(s) responsible Ophthalmology, Microbiology, Pharmacy for updating the guideline Uploaded to Intranet 24th July 2019 Buckinghamshire Healthcare NHS Trust

Guideline 372FM.5 16 of 16 Uncontrolled if printed