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Letter to the Editor

Outcomes of Patients with Herpes Simplex Keratitis Before and After the Implementation of a New Treatment Guideline in Sydney, Australia

Cabrera-Aguas, Maria PhD, MBBS; Kerdraon, Yves FRANZCO; Watson, Stephanie L. PhD, FRANZCO

Author Information
Asia-Pacific Journal of Ophthalmology: March-April 2021 - Volume 10 - Issue 2 - p 228-229
doi: 10.1097/APO.0000000000000368
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To the Editor:

Herpes simplex keratitis (HSK) is a significant cause of unilateral blindness in the developed world due to stromal opacification.1 The Herpetic Eye Disease Study Group made considerable recommendations for HSK treatment regimens in the 1990s.2 These recommendations have been poorly translated to clinical practice in Australia as they did not include topical aciclovir for epithelial HSK, which is easily accessible and commonly prescribed in Australia, and made no recommendations for keratouveitis or endothelial HSK.3 At Sydney Eye Hospital, in Sydney, Australia, a treatment guideline was developed using the Registered Nurses’ Association of Ontario Toolkit.4 This toolkit illustrates a systematic, well-planned, easy-to-follow implementation process to assist health professionals in creating evidence-informed clinical guidelines in any setting.4 This is based on the “Knowledge-to-Action” Framework that has the following 2 parts: the knowledge creation and the action cycle.5 We aimed to report the outcomes of patients with HSK before and after the guideline implementation at Sydney Eye Hospital.

A retrospective case review of all HSK patients from 2012 to 2013 and an audit postguideline implementation from June 1 to November 30, 2017 were conducted. Cases were identified from herpes simplex virus polymerase chain reaction swab results, pharmacy records, and hospital coding data. Clinical details were collated from medical notes. Ethics approval was obtained from the “South Eastern Sydney Local Health District” Human Resources Ethics Committee (HREC 13/296) and the tenets of the Declaration of Helsinki were adhered to.

Antiviral indication was classified as “therapeutic” or “prophylactic.” For patients with multiple HSK presentations in each study, only the first HSK presentation was included. The outcome was determined when the initial antiviral therapy was stopped or changed. For therapeutic indication, the outcomes were classified depending on the clinical response as “resolved,” “partially resolved,” or “worsened.” For prophylactic indication, “success” was recorded when an eye had no further HSK episodes and “failure” as an eye with an occurrence of a HSK episode. Therapeutic cases were divided in 2 groups: epithelial HSK and other HSK. Other HSK included stromal HSK with/without ulceration, endothelial HSK, keratouveitis, and patients with prior corneal graft.

The retrospective case review included 296 patients and the audit 85 patients. An outcome was determined for 210 patients in the case review and for 62 in the audit. The remaining patients from each study were excluded from analysis as they were lost to follow-up or were found not to have HSK at a subsequent review; therefore, a clinical outcome could not be determined.

The proportion of each outcome in patients with epithelial HSK, other HSK, and HSK prophylaxis preguideline versus postguideline implementation is shown in Table 1. An association between outcomes and adherence to recommendations preguideline and postguideline implementation was not found for epithelial HSK (P = 0.5) and other types of HSK (P = 0.4), but was significant for prophylactic therapy with oral valaciclovir 500 mg once daily (P = 0.009; Table 1). Comparing the outcomes between the preguideline and postguideline implementation studies, there was no statistically significant difference for any of the therapeutic groups. A reason may be that the number of patients with an outcome in the audit was too small to compare, especially for patients with prior graft, stromal HSK without ulceration, and endothelial HSK. In contrast, there was a statistically significant difference in the recurrence rate for the HSK prophylaxis group. The recurrence rate was 0% in the audit compared with 28% in the retrospective review. This may be because the indications and antiviral recommendations for HSK prophylaxis were unambiguous to clinicians for adopting them. Moreover, the audit only included 6-month data that is a short period to evaluate HSK recurrence as HSK prophylaxis is recommended for at least 1 year.6

TABLE 1 - Outcomes Versus Type of Antiviral Therapy Indication Pre- and Post-HSK Guideline Implementation
Preguidelines [n (%)] Postguidelines [n (%)] P Value
Epithelial HSK 0.5
 Resolved 41/83 (49) 12/19 (63)
 Partially resolved 39/83 (47) 6/19 (32)
 Worsened 3/83 (4) 1/19 (5)
Other HSK 0.4
 Resolved 4/15 (27) 1/1 (100)
 Partially resolved 8/15 (53) 0
 Worsened 3/15 (20) 0
 Resolved 2/11 (18) 1/6 (17)
 Partially resolved 6/11 (55) 4/6 (67)
 Worsened 3/11 (27) 1/6 (17)
Endothelial HSK
 Resolved 3/11 (27) 0
 Partially resolved 8/11 (73) 3/3 (100)
 Worsened 0 0
 Resolved 9/36 (25) 4/10 (40)
 Partially resolved 21/36 (58) 6/10 (60)
 Worsened 6/36 (17) 0 (0)
Prior corneal graft
 Resolved 7/18 (39) 1/1 (100)
 Partially resolved 8/18 (44) 0 (0)
 Worsened 3 /18 (17) 0 (0)
HSK prophylaxis 0.009
 Success 26/36 (72) 100 (22/22)
 Failure 10/36 (28) 0
n indicates the number of patients; SHSK-U, stromal herpes simplex keratitis without ulceration; SHSK+U, stromal herpes simplex keratitis with ulceration.

In conclusion, the implementation of the HSK treatment guideline contributed to the reduction of HSK recurrences in patients on HSK prophylaxis. Ongoing distribution of the guideline to the new staff and reminders to old staff is essential to maintain the adherence to this guideline. Audits every 2–3 years are warranted to evaluate the adherence to this guideline and outcomes.


1. Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf 2007; 5:240–250.
2. Sudesh S, Laibson PR. The impact of the herpetic eye disease studies on the management of herpes simplex virus ocular infections. Curr Opin Ophthalmol 1999; 10:230–233.
3. Cabrera-Aguas M, Kerdraon Y, Symes RJ, et al. Development, implementation, and evaluation of treatment guidelines for herpes simplex keratitis in Sydney, Australia. Cornea 2020; 39:834–840.
4. Registered Nurses’ Association of Ontario. Toolkit: Implementation of Best Practice Guidelines. Toronto, ON: Registered Nurses’ Association of Ontario; 2012.
5. Graham ID, Logan J, Harrison MB, et al. Lost in knowledge translation: time for a map? J Contin Educ Health Prof 2006; 26:13–24.
6. Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Arch Ophthalmol 2000; 118:1030–1036.
Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.