hAMT in infectious disease are generally based on the antimicrobial and anti-inflammatory advantages of hAM. Antimicrobial activity is associated with the presence of several components in the amniotic fluid, including lysozyme, transferrin, and immunoglobulin [1]. Additionally, studies have shown that hAM can act as an effective reservoir of antimicrobials and provide sustained medication in compiled treatment [9]. Anti-inflammatory function of hAM ensues through regulation of T cell function and anti-inflammatory secretion [10].
In the literature, microbial keratitis due to several causative microorganism has been reported to be treated with hAMT. Herpetic keratitis is one of these infectious keratitis categories. 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 benefits 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.
Resistant bacterial keratitis is another indication for hAMT. In previous studies, successful results as immediate pain relief and epithelial recovery in patients with bacterial keratitis who were treated by topical antibiotics and hAMT was reported [7]. In the present study, patients with proven causative agents received appropriate treatment, while patients with unknown causative agents were treated with empirical antibiotic therapy, and the majority showed a recovery response to combined antimicrobial and hAMT treatment. Both eyes of one patient, who was receiving immunosuppressive treatment for terminal stage oropharyngeal squamous cell cancer, hAMT was unsuccessful.
In fungal keratitis, in which pathogens usually infiltrates deep layers of cornea, hAMT may not be effective. In such cases, antifungal treatment may also be insufficient due to the minimal corneal stromal penetration of topical antifungal medications[14]. Chen et al [15] showed that in fungal corneal ulcers, amniotic membrane lysis was prominent and 25% of the cases required keratoplasty. In the present study, in one fungal (Fusarium solani) keratitis patient, who had a history of organic based trauma, combination of hAMT and antifungal therapy were ineffective. Patient underwent two therapeutic keratoplasty surgery in order to control infection.
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.
There are several factors such as ulcer size and inflammation grade, effecting the hAMT success in infectious keratitis beside the causative microorganism. Abdulhalim et al [18] and Chen et al [15] reported the success rates as 90% and 83%, in average ulcer sizes of 5.45 ± 1.73 mm and 5.43 ± 2.61 mm, respectively. In the present study, hAMT success rate was observed to be 76.9% with an average ulcer size of 9.7 (4.5–12) mm, which is consistent with the estimated efficiency according to the previous reports in a larger average ulcer size.
Another factor that may affect the hAMT success in infectious keratitis is the time duration between the presentation and hAMT intervention. 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. In this direction, the cases in which hAM application was performed in the first 7 days of the presentation tends to be successful in order to control the infection and promote wound healing than the cases in which hAMT was performed after the 7 days of presentation. Moreover, average recovery time was prolonged after hAMT which was performed after the first 7 days of presentation. This observation reveals that an initial hAMT within 2 weeks of the therapy may probably support decrease inflammation, induce healing of infectious ulcers.
The facilitating effect of antimicrobial agent maintenance and its tectonic features are also prominent for the hAMT usage in infectious keratitis. Although, the more prolonged residency of hAM on ocular surface may provide better results in especially inflammatory situations, membrane dissolvement becomes faster due to the increased proteolytic features of the ocular surface[19] [20]. Kheirkhah at al [21] revealed the amniotic membrane lysis time as 5.8 ± 1.2 days (range, 4 to 8 days) in microbial keratitis. In the present study, the residence time of the amniotic membrane on the ocular surface was a slight longer with 13.3 days of average. The higher success rate of the present study may be attributed to this longer the amniotic membrane residence time on the ocular surface. Also, in severe cases of keratitis, it may be necessary to repeat hAMT in order to provide extended properties of hAM on healing time [7]. In the present study, average hAMT surgery was 1,46 for each eye.
Additionally, hAM has reported to be have an effect of shortening the healing time with 4.08 days of average in microbial keratitis[13]. Zeng et al. [22] showed that the average healing time was statistically shorter in the hAMT group (6.89 ± 2.98d), compared to the control group (10.23 ± 2.78d). In the present study average healing time of 32.1 (6–57) days with hAMT was found to be consistent with the previous literature.
Moreover, there is a pain relief advantage of hAMT. This relief has been attributed to the biological patch feature and anti-inflammatory effects of the membrane [23]. In the present study, the mean hospitalization time was shortened after hAMT. hAM facilitates outpatient follow up of the patient by acting as a biological bandage for tectonic purposes, which may prevent the patient form additional resistant hospital-based infections, maintain the antimicrobial agent presence on the ocular surface and relieving the pain.
In conclusion, hAM application in infectious keratitis can be performed in the early period without waiting for the sterile phase following antimicrobial treatment with relatively higher success possibility. Its antimicrobial, and anti-inflammatory features facilitate the control of the disease. Also, hAMT usage in infectious keratitis shortens the healing and hospitalization time.