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

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

Effectiveness of adjuvant photoactivated chromophore corneal collagen cross-linking versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of adjuvant photoactivated chromophore for keratitis - corneal collagen cross-linking (PACK-CXL) versus standard antimicrobial treatment alone for corneal healing in patients with infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause for corneal blindness globally. Broad-spectrum antimicrobial therapy is currently the standard treatment, but there is a growing need for alternative or adjuvant antimicrobial treatment, due to the emerging antimicrobial resistance, long treatment duration and cost of treatment. Photoactivated chromophore for keratitis - corneal collagen cross-linking has been increasingly used as an adjuvant treatment for infectious keratitis but high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients with infectious keratitis, encompassing bacterial, fungal, acanthamoeba, viral, mixed or culture-negative presumed infectious keratitis cases. Patients who have a previous history of infectious keratitis before the study or those that had less than seven days' follow-up from the start of the treatment will be excluded. METHODS: The electronic databases to be searched will include MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Only English articles will be included. Titles, abstracts and full text of the relevant studies will be assessed by two independent reviewers. The extracted data will include specific details about the study, including authors and study title, year of publication, sample size, populations, and study methods. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities in the reporting of outcome measures. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019131290

Effectiveness and safety of early adjuvant amniotic membrane transplant versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of early adjuvant amniotic membrane transplant versus standard antimicrobial therapy for infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause of corneal blindness worldwide. Broad-spectrum topical antimicrobial therapy is currently the gold standard for treatment. Amniotic membrane transplant has been employed as an adjuvant therapy to promote corneal healing; however, high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients of all ages with all types of infectious keratitis, including bacterial, fungal, viral, acanthamoeba, mixed, and culture-negative presumed infectious keratitis. The authors will exclude patients who have undergone other types of primary surgery other than amniotic membrane transplant during the initial management and those who had less than seven days' follow-up from the commencement of the treatment. METHODS: Electronic databases, including MEDLINE, Embase, Cochrane CENTRAL, and relevant registries, will be searched for pertinent studies. Titles, abstract, and full text of the relevant studies will be independently assessed by two reviewers. Extracted data will include authors, year of publication, sample size, types of amniotic membrane transplant techniques, types of causative microorganisms, main outcomes, visual acuity, and adverse events. No restriction will be applied to the date or language. Bibliographies of the included articles will be independently and manually screened by two authors to identify further relevant studies. Eligible studies will be critically appraised by two independent reviewers for methodological quality. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities. SYSTEMATIC REVIEW REGISTRATION NUMBER: This systematic review has been registered with PROSPERO (CRD42020175593)

Corneal Neurotization for Neurotrophic Keratopathy: Clinical Outcomes and In Vivo Confocal Microscopic and Histopathological Findings

Purpose: To describe the long-term outcomes and in vivo confocal microscopic (IVCM) and histopathological findings after corneal neurotization surgery. / Methods: We included 2 patients who underwent corneal neurotization surgery for severe unilateral neurotrophic keratopathy secondary to cerebellopontine angle meningioma. Corneal sensation was measured using the Cochet–Bonnet esthesiometer (CBE) (0–60 mm). IVCM was performed using the Heidelberg HRT3 Rostock Corneal Module. Histopathological examination was performed on the excised corneoscleral disc of patient 2. / Results: In patient 1, corneal sensation improved from 0 mm preoperatively to 60 mm in all 4 quadrants by 2 years postoperatively and was maintained at 5 years postoperatively with identifiable subbasal and stromal corneal nerves on IVCM. In patient 2, corneal sensation improved from 0 mm preoperatively to 10 mm in 3 quadrants (9 months postoperatively) but returned to 0 mm in all quadrants by 2 years postoperatively. IVCM failed to identify any subbasal and stromal corneal nerves. At 5 years postoperatively, evisceration was performed to ameliorate uncontrolled and persistent ocular pain and poor cosmesis. Histopathological examination of the excised corneoscleral disc confirmed the presence of normal-sized, central corneal stromal nerve fascicles but without direct continuity with the transplanted perilimbal nerve bundles. / Conclusions: Our study elucidates the mechanism of corneal neurotization surgery at a cellular level. Although only 1 patient achieved long-term improvement in corneal sensation postoperatively, the findings on IVCM and histopathological examination suggest that partial regeneration/maintenance of corneal nerves after corneal neurotization surgery is likely attributed to the paracrine neurotrophic support, instead of direct sprouting, from the perilimbal transplanted nerve fascicles

Topical antibiotics for treating bacterial keratitis: a network meta-analysis

This is a protocol for a Cochrane Review (prototype). The objectives are as follows: To compare the effectiveness and safety of topical antibiotics for treating BK and to rank different interventions through a systematic review and NMA