A Challenging Management of Pseudomonas Perforated Corneal Ulcer with Multilayer Amniotic Membrane Transplantation and Pericardial Patch Graft in Pediatric Patient

Introduction: Pseudomonas aeruginosa (P. aeruginosa) is the leading cause of corneal ulcers in children 0 to 3 years of age compared to children in general. Case presentation: A two-monthsold infant presented with whitish patches on the right eye two days before admission. A central corneal ulcer with a size of 7-mm x 7-mm accompanied by corneal thinning and melting was shown on the right cornea. It is was surrounded by greyish white creamy infiltrates. Corneal scraping showed Pseudomonas aeruginosa specimens. The cornea became perforate and crystalline lens extrusion was found at the day after intravenous ceftriaxone, levofloxacin eye drop, and cefazoline fortified eye drop administering. It might be caused by bacterial elastase and toxin which contributed to corneal damage. The patient was underwent a multilayer Amniotic Membrane Transplantation (AMT) combined with a pericardial patch graft due to corneal perforation. Two months post-AMT and pericardial patch graft the corneal perforation became entirely heal due to multilayer AMT, despite lysis of the pericardial patch graft. Corneal scar formation and reduction of vitreous opacity in ultrasound examination were shown. The patient was planned to undergo keratoplasty. Conclusions: Corneal ulcers due to Pseudomonas aeruginosa are highly destructive. The levels of infection, diagnostic, and therapeutic are still problems in pediatric patients. Lens extrusion and lysis of the pericardial patch graft are examples in this case. Keratoplasty is the definitive treatment for corneal ulcers with perforation; however, multilayer AMT combined with pericardial patch graft can be used as an alternative therapy to accelerate wound healing, reduce inflammation, and maintain the integrity of the eyeball.


Introduction
Corneal ulcer is an infectious condition of the cornea that disrupts the epithelial layers involving the corneal stroma. Corneal ulcers are one of the leading causes of monocular blindness after untreated cataracts in many developing countries in Asia, Africa, and the Middle East. [1] According to the World Health Organization [2] , approximately 700.000 children each year have a pathological condition of the cornea that permanently affects vision. The incidence of blindness due to keratitis in children is twenty times higher in the tropics and developing countries. Eye trauma is the leading predisposing cause of keratitis in children in 26-58% of cases. Several studies before 2000 showed that trauma (21.1-44.0%), systemic disease (14.0-30%), ocular surface disease (17.7-22.7%), and history of surgery on the anterior segment (8.8-24.0%) were the causes of keratitis. [3] In addition, studies in the United States, India, and Taiwan [2], [4] have shown that contact lens wear and environmental factors also play a role in causing keratitis.
The spectrum of micro-organisms causing corneal ulcers varies depending on geographic location. The most common cause of corneal ulceration is keratitis caused by bacteria, fungi, viruses, and protozoa, which is established https://e-journal.unair.ac.id/VSEHJ based on clinical practice examination by supporting microbiological staining or culture of corneal tissue.

Staphylococcus aureus and Streptococcus pneumoniae
are gram-positive micro-organisms, and Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative microorganism mainly causing keratitis, especially in children.
Pseudomonas aeruginosa and α-hemolytic streptococci are the leading causes in children aged 0 to 3 compared to children in general, and the incidence in children <3 years of age is two times higher than in children of other ages. [2], [5]- [6] Pseudomonas aeruginosa, Coagulase-negative staphylococci, and Staphylococcus aureus are the causes of contact lens-related keratitis in children.
Pseudomonas aeruginosa is a gram-negative rod that thrives in moist environments such as water and soil.
In children, Pseudomonas aeruginosa is an opportunistic pathogen associated with damage to the corneal tissue due to trauma, prematurity, and contact lens wear. The pathophysiology of Pseudomonas aeruginosa infection in children is influenced by virulence factors, namely glycocalyx, pili, flagella, endotoxins and exotoxins, and bacterial enzymes. These factors can interfere with protein synthesis and damage cell membranes. [7] The goals of treating corneal ulcers in children are eradicating infection with antimicrobials, preventing scarring, and preventing visual disturbances. As opposed to adults, surgical management is rarely required in children except in impending perforation and corneal perforation. Surgical actions that can be done are cyanoacrylate glue, therapeutic penetrating or lamellar keratoplasty, conjunctival flap, debridement, and amniotic membrane transplantation. [6] This case report discusses the detailed steps of examination, diagnosis, and medical and surgical management of Pseudomonas corneal perforation in pediatric patients.

Case presentation
A two-month-old infant presented with whitish patches on the right eye two days before admission.
The patient complained about swollen, red, watery, and yellow discharge on his right eye on the first day. He was then brought to a general practitioner in the local community health center and was given a chloramphenicol eye ointment. The next day, the condition worsened with whitish patches on his right eye. The patient was then referred to and hospitalized in Dr. Saiful Anwar General Hospital.
The patient is the third child of three siblings with a history of the second child dying prematurely. Based on the mother's antenatal care (ANC) for monthly checkups to an obstetrician, there is no history of fever, sore throat, vaginal discharge, or infections in the genital area.
There was no history of consuming alcohol, cigarettes, or drugs. The baby's delivery was through cesarean section at 36 weeks of gestation, with good condition, weighing 2.100 grams and immediately crying. The patient showed normal development and growth according to age, and he has completed basic immunization standards. There is no history of the same disease in the family and no history of trauma to the eye.  Two days after the admission, an examination of the right eye revealed a spontaneous corneal perforation with lens prolapse. Palpebral hyperemia and chemosis, pericorneal injection, and mucopurulent secretions increased compared to the previous day ( Figure 2).
Based on clinical findings, the patient was planned for keratoplasty; however, no available donor was found. Therefore, the patient was treated surgically with an amniotic membrane graft combined with a pericardial patch graft. First, we performed a 360-degree peritomy,   The patient was discharged on the next day.

Discussion and conclusions
Corneal ulcer or ulcerative keratitis is an inflammatory or infectious condition of the cornea that involves disruption of the epithelial lining with involvement of the corneal stroma. Pseudomonas aeruginosa infection is common in young children. In children under three years of age, more than 50% of cases have been caused by Pseudomonas aeruginosa. Pseudomonas aeruginosa usually presents as a condition in which bacteria multiply rapidly, resulting in the inflammation of the epithelium with edema, ulceration of the stroma, and can cause significant stromal tissue damage, ending in loss of vision. [5], [8] Pseudomonas aeruginosa is an aerobic gram-negative bacillus that grows in temperatures ranging from 30-37°C and shows gray or greenish colonies. Infections caused by these organisms are generally fulminant. ExoT is an adenosine diphosphate ribosyltransferase that interferes with actin cytoskeletal regulation and inhibits phagocytosis, thereby increasing the survival of Pseudomonas aeruginosa. [6], [9]  The clinical manifestations of corneal ulcers vary widely, including red eyes, pain, decreased vision, tearing, photophobia, discharge, and swollen eyelids.
The onset of fungal ulcers is quieter than Pseudomonas aeruginosa, which grows and develops rapidly. [6] Slit- underlying cause. [6], [9], [10], [11] In this case, the cause of corneal ulcers is challenging reduce pain and synechiae. [11], [12], [13] From several studies, the main antibiotics used for Fosfomycin, and polymyxin (colistin, polymyxin B). [14] Sikha Gupta et al. [15] stated that Gatifloxacin showed significant activity against pseudomonal strains followed by ciprofloxacin and tobramycin. The study also reported that Pseudomonas aeruginosa was sensitive to the cephalosporin group, namely ceftazidime (39%), cefuroxime (37%), and cefazolin (32%). A report from the UK has found Pseudomonas aeruginosa to be 100% sensitive to moxifloxacin and 99% to ciprofloxacin. In this case, the corneal ulcer developed into a corneal perforation, and a keratoplasty was planned, but there were limitations-the unavailability of a corneal donor.
Other options have been carried out, such as the surgical management of multilayer AMT and pericardial patch graft with an indication of corneal perforation due to corneal ulcers caused by the Pseudomonas aeruginosa bacteria.
The surgical treatment of corneal ulcers is based on size, location, and cause. Especially in perforated corneal ulcers, surgical intervention is required to close the perforation, repair the chambers of the eye, and restore visual function. Corneal gluing is suitable for corneal perforations of less than 2 mm. Pericardial patch graft is a membrane that has been designed to support, repair, and replace the structure and action of connective tissue and regenerate tissue. [13], [16] AMT can provide structural support in areas of corneal there is a failure of medical treatment and large corneal perforation. [13], [17], [18] Potential subretinal or subchoroidal hemorrhages). [19], [20], [21] It is difficult to perform an eye examination in children, mainly when calculating the size and depth of the corneal ulcer, as it is essential for determining the management and evaluation of the corneal ulcer.
This case report illustrates that concentrations Establishing a diagnosis of corneal ulcers due to Pseudomonas aeruginosa in children is a challenge in itself during history-taking and physical examination. Thus, the role of cultural examination is crucial. Corneal ulcers due to Pseudomonas aeruginosa are highly destructive. The levels of infection, diagnostic, and therapeutic problems in pediatric patients may differ from those in adults.
Lens extrusion and lysis of pericardial patch grafts serve as an example in this case. Keratoplasty is the definitive treatment for corneal ulcers with perforatio; however, multilayer AMT combined with pericardial patch graft can be used as an alternative therapy to accelerate wound healing, reduce inflammation, and maintain the integrity of the eyeball.