Abstract

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (− 4.08 days; 95% CI − 6.27 to − 1.88; p < 0.001) and better UDVA (− 0.26 logMAR; − 0.50 to − 0.02; p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46–1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable.

Highlights

  • The systematic review protocol was registered with PROSPERO and The Joanna Briggs Institute of Evidence ­Synthesis[80]

  • Two authors (D.S.J.T and C.H.) searched MEDLINE (January 1950 to November 2020), EMBASE (January 1980 to November 2020), Cochrane Central Register of Controlled Trials (CENTRAL), ISRCTN registry, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for primary research related to amniotic membrane transplantation (AMT) for IK

  • Electronic databases were first searched on 01 March 2020, followed by a final update on 01 November 2020

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Summary

Methods

The systematic review protocol was registered with PROSPERO (registration number: CRD42020175593) and The Joanna Briggs Institute of Evidence ­Synthesis[80]. Two authors (D.S.J.T and C.H.) searched MEDLINE (January 1950 to November 2020), EMBASE (January 1980 to November 2020), Cochrane Central Register of Controlled Trials (CENTRAL), ISRCTN registry (www.isrctn.com/editAdvancedSearch), US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (http://clinicaltrials.gov) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp) for primary research related to AMT for IK. There was no date or language restriction in the search for trials. Electronic databases were first searched on 01 March 2020, followed by a final update on 01 November 2020. Search strategies for MEDLINE and EMBASE are provided in the Supplemental Table S1

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