Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

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.

Impact of Adjuvant Amniotic Membran Transplantation In Infectious Ulcerative Keratitis

“…Acanthamoeba infection is one of the most feared keratitis types especially in contact lens wearers. hAMT was reported to be effective in patients with Acanthamoeba keratitis [13] [16] [17]. In the present study, one patient with Acanthamoeba keratitis had an absolute recovery response after hAMT additionally to appropriate medical therapy.…”

“…In herpetic keratitis, associated neurotrophic keratopathy, causes delay in corneal healing [11] [12] .Therefore, hAMT serves as a useful adjunctive therapy by inducing corneal epithelial regeneration in this clinical situation. Although the bene ts in herpetic keratitis have not been established in randomized controlled trials, a high rate (94%) of complete corneal healing was demonstrated [13]. In the present study, healing response was reported to be 100% in herpes keratitis patients.…”

“…It was emphasized that in clinical practice, hAMT usage tends to be reserved as a second-line therapy in infectious keratitis, mainly to promote cornea healing in non-healing ulcer after the sterilization phase. Thus, the value of using hAMT in addition to antimicrobial treatment during the active phase of infectious keratitis remains still uncertain [13]. In the present study, it was aimed to evaluate the antimicrobial effect of hAM on wound healing without waiting for the sterile phase of the infectious keratitis.…”

Risk Factors, Clinical Outcomes, and Prognostic Factors of Bacterial Keratitis: The Nottingham Infectious Keratitis Study

“…Additionally, we showed that corneal healing was negatively affected by older age, larger infiltrate size and poorer presenting vision. Gaining a better knowledge of these prognostic factors may enable earlier interventions (e.g., temporary tarsorrhaphy or amniotic membrane transplant) to help promote corneal healing and re-epithelialisation (32)(33)(34)(35). The poorer corneal wound healing in older patients with BK is likely related to the presence of co-existing ocular surface diseases (e.g., dry eyes, neurotrophic keratopathy, and others), immunosuppression and the age-related reduction in proliferative ability of the limbal stem cells (36)(37)(38).…”

Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies

“…(Shah et al, 2011;Khor et al, 2018;Ting et al, 2018;Ting et al, 2019a;Green et al, 2019;Khoo et al, 2020;Ting et al, 2021b;Hoffman et al, 2021) Broadspectrum topical antibiotic treatment is the current mainstay of treatment for IK, but the management is being challenged by the low culture yield, (Ting et al, 2021a;Ting et al, 2021b) polymicrobial infection, (Tu et al, 2009;Ting et al, 2019b;Khoo et al, 2020) and emerging AMR. (Hernandez-Camarena et al, 2015;Lalitha et al, 2017;Lin et al, 2019;Asbell et al, 2020) In addition, adjuvant procedures/surgeries such as therapeutic corneal cross-linking, (Ting et al, 2019c) amniotic membrane transplantation, (Ting et al, 2021c) and therapeutic/tectonic keratoplasty (Hossain et al, 2018;Ting et al, 2020a) are often required to manage uncontrolled infection and its complications, including corneal melting and perforation. All these issues highlight the need for new treatment for IK.…”