Corneal Perforation Repair Using a Novel Lyophilized Amniotic Membrane Graft Technique: Plug and Patch.

BACKGROUND The use of amniotic membranes for corneal perforations using different surgical techniques has been widely described in the literature. This case report is a novel variation in the technique that can be useful for incorporating in clinical practice when the need arises. CASE REPORT A 36-year-old male patient presented to our clinic with a corneal ulcer in his left eye caused by herpetic keratitis, treated with a topical non-steroidal anti-inflammatory (indomethacin 0.1% solution). Examination revealed a paracentral 2-mm wide corneal perforation on the site of the corneal ulcer. The patient was admitted to the hospital. He was treated with intravenous piperacillin-ofloxacine, and an emergency surgical intervention using a lyophilized amniotic membrane was performed using a "plug and patch" technique. Postoperatively, the patient received 48 h of intravenous antibiotics and was discharged on topical antibiotic/corticosteroid eyedrops along with a 10-day course of oral antibiotics (ofloxacin) and antiviral therapy (valaciclovir). Three months after surgery, the anterior chamber was formed, the corneal defect was closed, and visual acuity improved. One year after initial presentation, anterior segment optical coherence tomography showed a large scarred but healed cornea. CONCLUSIONS We report the successful use of combination of a single round-shaped rolled amniotic membrane with a multilayered amniotic membrane transplantation for the treatment of a 2-mm-wide perforated corneal ulcer. This technique allowed for preservation of the globe integrity without the need for a keratoplasty, stopped further tissue loss, and was associated with a rapid visual recovery.

Perforación de la córnea: una complicación poco común del traumatismo del nacimiento / Corneal perforation: A rare complication of birth trauma

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Development of an In Situ Printing System With Human Platelet Lysate-Based Bio-Adhesive to Treat Corneal Perforations.

Purpose: Corneal perforation is a clinical emergency that can result in blindness. Currently corneal perforations are treated either by cyanoacrylate glue which is toxic to corneal cells, or by using commercial fibrin glue for small perforations. Both methods use manual delivery which lead to uncontrolled application of the glues to the corneal surface. Therefore, there is a need to develop a safe and effective alternative to artificial adhesives. Methods: Previously, our group developed a transparent human platelet lysate (hPL)-based biomaterial that accelerated corneal epithelial cells healing in vitro. This biomaterial was further characterized in this study using rheometry and adhesive test, and a two-component delivery system was developed for its application. An animal trial (5 New Zealand white rabbits) to compare impact of the biomaterial and cyanoacrylate glue (control group) on a 2 mm perforation was conducted to evaluate safety and efficacy. Results: The hPL-based biomaterial showed higher adhesiveness compared to commercial fibrin glue. Treatment rabbits had lower pain scores and faster recovery, despite generating similar scar-forming structure compared to controls. No secondary corneal ulcer was generated in rabbits treated with the bio-adhesive. Conclusions: This study reports an in situ printing system capable of delivering a hPL-based, transparent bio-adhesive and successfully treating small corneal perforations. The bio-adhesive-treated rabbits recovered faster and required no additional analgesia. Translational Relevance: The developed in situ hPL bio-adhesives treatment represents a new format of treating corneal perforation that is easy to use, allows for accurate application, and can be a potentially effective and pain relief treatment.

Evaluation and Clinical Course of Keratomalacia With Descemetocele in a Child With Autism and Vitamin A Deficiency.

Autistic children with selective diets have an elevated risk for vitamin A deficiency. The authors present the case of a 7-year-old boy with keratomalacia resulting from dietary vitamin A deficiency. Optical coherence tomography and ultrasound biomicroscopy can provide useful details of the cornea and underlying structures. Vitamin A supplementation can result in significant resolution, obviating the need for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2020;57:e1-e3.].

Mechanism of fluid leak in non-traumatic corneal perforations: an anterior segment optical coherence tomography study.

AIM: Non-traumatic corneal perforations (CPerfs) may present with shallow/flat or formed anterior chamber (AC). This study uses anterior segment optical coherence tomography (ASOCT) to ascertain these differences. METHOD: The study included 14 eyes of 13 patients. They underwent high-resolution ASOCT scans at multiple time points, prior to and after cyanoacrylate glueing, between January 2016 and July 2018. A retrospective analysis of over 2500 ASOCT sections and AS photographs was conducted by two independent observers. The findings were correlated with clinical features and diagnoses. RESULT: All patients had documented Seidel's positive sign at the outset. Two groups with distinctive features were identified. In group 1, 'formed' AC, there was hydration of the cornea with lamellar separation of the stroma, intrastromal pockets of fluid, epithelial bullae and an indirect communication between AC and the exterior. In group 2, 'flat' AC, the corneal hydration was less obvious, there were no pockets of intrastromal fluid, no epithelial bullae and a direct communication of the AC with the exterior. After glueing, the stromal hydration resolved, and healing occurred beneath the glue. The glue and corneal blood vessels consistently cast a dense shadow posteriorly on ASOCT. CONCLUSION: ASOCT demonstrates that leaking CPerfs can be indirect or direct. The former is associated with a 'formed' AC and the latter with a very shallow/flat AC. The valvular nature of the communication in indirect perforations allows the AC to maintain its volume despite a continuous leak.

In Vitro Antifungal Effect of Acrylic Corneal Glue (N-Butyl-2-Cyanoacrylate).

PURPOSE: The purpose of this study was to evaluate the in vitro antifungal effects of n-butyl-2-cyanoacrylate (nB2CA; Histoacryl Blue; B. Braun, Melsungen, Germany) against a variety of different fungal species. METHODS: Inocula taken from suspensions prepared with Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus ochraceus, Aspergillus oryzae, Fusarium solanii, Fusarium oxysporum, Trichoderma spp., Rhizomucor spp., Scedosporium apiospermum, Penicillium commune, Phoma glomerata, and Chrysosporium spp. molds and Candida albicans, Candida glabrata, Candida parapsilosis, Candida kruzei, Candida dubliniensis, Candida tropicalis, Candida kefyr, and Trichosporon asahii yeasts were spread on the surface of RPMI1640 agar media. Then, 50 µL of nB2CA was dropped on the surface of these media and they were incubated at 35°C. Observation of a clear zone of inhibition around the nB2CA was regarded as an indicator of the susceptibility of the fungi to nB2CA, and the absence of this zone was interpreted as an indicator of nonsusceptibility. The inhibition zone diameter was measured across the largest clear zone. RESULTS: A zone of inhibition was observed around nB2CA for all of the yeast and mold species except A. flavus, A. oryzae, and Chrysosporium spp. Among molds, the largest zone of inhibition was observed with P. glomerata (25.7 ± 0.6 mm), whereas among yeasts, the largest zone of inhibition was observed with C. kruzei (19.3 ± 1.5 mm). CONCLUSIONS: nB2CA has shown antifungal activity against 18 different mold and yeast species, but not against A. flavus, A. oryzae, and Chrysosporium spp. molds.

Acute Glaucoma Following Cyanoacrylate Glue Patch for Corneal Perforation.

PURPOSE: To describe a case of acute glaucoma after cyanoacrylate gluing for a nontraumatic central corneal perforation. METHODS: A 55-year-old woman with history of rheumatoid arthritis and severe dry eye presented to emergency with a right central corneal perforation. She was treated successfully with the use cyanoacrylate glue patch but iridocorneal adhesions remained. The next day she presented with ocular pain, headaches, and vomiting. On examination she had shallow anterior chamber (AC) with no aqueous leakage but her intraocular pressure (IOP) was 56 mm Hg measured with rebound tonometry. An anterior segment optical coherence tomography scan showed a 360 degrees central iris adhesion with shallow AC. Topical and oral treatment for acute glaucoma was given that decreased her IOP. She then underwent urgent surgery to release the iridocorneal adhesions and restore aqueous flow that was achieved without replacing the glue patch. RESULTS: One day postoperatively her right eye was comfortable and her IOP measurement remained within normal limits. The AC was deep with no iridocorneal adhesions. CONCLUSIONS: Close monitoring of the IOP is recommendable in central corneal perforations with iris adhesions managed with cyanoacrylate glue due to the potential developing of aqueous blockage.

Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations.

PURPOSE: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. METHODS: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-µm thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. RESULTS: Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 µm hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3/10) cases. CONCLUSIONS: An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.

Cyclosporine for Dry Eye Associated With Nivolumab: A Case Progressing to Corneal Perforation.

PURPOSE: To present the clinical outcome of 2 cases of severe dry eye associated with Nivolumab, with 1 case progressing to corneal perforation. DESIGN: Case report. CASE 1: : A 58-year-old man with metastatic melanoma was referred for the management of severe bilateral dry eyes after undergoing his sixth cycle of Nivolumab. The right eye progressed to corneal perforation 4 weeks after referral, after which Nivolumab was discontinued. When metastatic disease recurred, Nivolumab was continued with an ocular surface stabilized with an intensive regimen that included topical cyclosporine. CASE 2: : A 46-year-old woman with metastatic melanoma was referred for severe dry eye symptoms around the timing of her third cycle of Nivolumab. Improvement of symptoms and surface staining was achieved with a regimen that included aggressive lubrication and topical cyclosporine. On follow-up after completing Nivolumab therapy, metastatic melanoma has remained regressed. CONCLUSIONS: Nivolumab can cause or worsen dry eye disease to the point of corneal perforation. Given that its antitumor effect is immune-mediated, therapies targeting ocular surface inflammation can be effective for stabilizing dry eye disease in patients who continue treatment with Nivolumab.

Recovery of the Corneal Stroma Associated With Rapid Reepithelialization Induced by the Fibronectin-Derived Peptide PHSRN in 2 Cases of Corneal Perforation Due to a Persistent Epithelial Defect.

PURPOSE: To report 2 cases of corneal perforation associated with a persistent epithelial defect (PED), which were treated with eye drops containing the fibronectin-derived peptide PHSRN (Pro-His-Ser-Arg-Asn). METHODS: A 67-year-old man and a 58-year-old man presented with corneal perforation associated with a PED caused by lagophthalmos. PHSRN eye drops were administered 4 times a day to both patients. RESULTS: Both patients experienced healing of the epithelial defect and closure of corneal perforation within 3 or 4 days after the onset of PHSRN treatment. Anterior segment optical coherence tomography also revealed recovery of corneal stromal thickness at the lesion site. CONCLUSIONS: PHSRN eye drops were effective for the treatment of corneal perforation due to the PED, with rapid reepithelialization being followed by full restoration of stromal thickness.

[Peripheral corneal melting syndrome in psoriatic arthritis treated with adalimumab]. / Síndrome da ceratomalácia (Corneal Melting) periférica na artrite psoriásica tratada com adalimumabe.

Peripheral corneal melting syndrome is a rare immune condition characterized by marginal corneal thinning and sometimes perforation. It is associated with rheumatic and non-rheumatic diseases. Few cases of peripheral corneal melting have been reported in patients with psoriasis. The pathogenesis is not fully understood but metalloproteinases may play a pathogenic role. Anti-TNF therapy has shown to decrease skin and serum metalloproteinases levels in psoriasis. We report a 61-year-old man with peripheral corneal melting syndrome associated with psoriatic arthritis who received Adalimumab to control skin and ocular inflammation. To our knowledge, this is the first case report of peripheral corneal melting syndrome in psoriatic arthritis treated with Adalimumab showing resolution of skin lesions and complete healing of corneal perforation in three months.

Síndrome da ceratomalácia (Corneal Melting) periférica na artrite psoriásica tratada com adalimumabe / Peripheral corneal melting syndrome in psoriatic arthritis treated with adalimumab

RESUMOA síndrome do corneal melting periférica é uma rara condição imune caracterizada por afinamento da margem da córnea e, às vezes, perfuração. Está associada a doenças reumáticas e não reumáticas. Poucos casos de síndrome do corneal melting periférica foram relatados em pacientes com psoríase. A patogênese não foi completamente entendida, mas as metaloproteinases podem ter papel patogênico. A terapia Anti-TNF diminuiu os níveis de metaloproteinases na pele e no sangue em psoríase. Reportamos o caso de um homem de 61 anos com síndrome do corneal melting periférica associada à artrite psoriásica que recebeu adalimumabe para controlar a inflamação na pele e no olho. Pelo que sabemos, este é o primeiro caso de síndrome do corneal melting periférica em artrite psoriática tratado com adalimumabe mostrando evolução nas lesões cutâneas e cura total da perfuração da córnea em três meses.

ABSTRACTPeripheral corneal melting syndrome is a rare immune condition characterized by marginal corneal thinning and sometimes perforation. It is associated with rheumatic and non-rheumatic diseases. Few cases of peripheral corneal melting have been reported in patients with psoriasis. The pathogenesis is not fully understood but metalloproteinases may play a pathogenic role. Anti-TNF therapy has shown to decrease skin and serum metalloproteinases levels in psoriasis. We report a 61-year-old man with peripheral corneal melting syndrome associated with psoriatic arthritis who received adalimumab to control skin and ocular inflammation. To our knowledge, this is the first case report of peripheral corneal melting syndrome in psoriatic arthritis treated with adalimumab showing resolution of skin lesions and complete healing of corneal perforation in three months.

Perforating corneal injury in rat and pentadecapeptide BPC 157.

Based on its healing effects in various tissues, we hypothesized that the stable gastric pentadecapeptide BPC 157 heals corneal ulcerations in rats and effects corneal transparency. We made a penetrant linear 2-mm incision in the paralimbal region of the left cornea at the 5 o'clock position with a 20-gauge MVR incision knife at 45° under an operating microscope. Medication was BPC 157 (2 pg/mL, 2 ng/mL, and 2 µg/mL distilled water, two eye drops/left rat eye) immediately after injury induction and then every 8 h up to 120 h; controls received an equal volume of distilled water. In contrast to the poor healing response in controls, BPC 157 significantly accelerated the healing process in 2 µg and 2 ng BPC 157-treated eyes, starting 24 h after the injury, and the fluorescein and Seidel tests became negative. The epithelial defects were completely healed at 72 h (2 µg BPC 157-treated group) and at 96 h (2 ng BPC 157-treated group) after injury. Aqueous cells were absent at 96 h and 120 h after injury in the 2 µg and 2 ng BPC 157-treated groups, respectively. In conclusion, BPC 157 effects the rapid regaining of corneal transparency. Whereas controls developed new vessels that grew from the limbus to the penetrated area, BPC 157-treated rats generally had no new vessels, and those that did form in the limbus did not make contact with the penetrated area. Thus, BPC 157 eye drops successfully close perforating corneal incisions in rats.

Modified lamellar keratoplasty and immunosuppressive therapy guided by in vivo confocal microscopy for perforated Mooren's ulcer.

AIM: To observe the efficacy of modified lamellar keratoplasty (LK) and immunosuppressive therapy guided by in vivo confocal microscopy (IVCM) for perforated Mooren's ulcer. METHODS: 25 patients (31 eyes) with perforated Mooren's ulcer underwent modified LK. The perforated hole was patched with a thin, fresh posterior cornea containing the endothelium, before a glycerin-preserved lamellar graft shaped like the defect was placed. Immunosuppressants and corticosteroids were used and their dosages adjusted following the density of dendritic cells in the corneal graft postoperatively as detected by IVCM. The anatomical recovery, visual acuity, surgical complications, and recurrence were followed up for 24 months. RESULTS: Favourable anatomical recovery was achieved in 27 eyes (87.1%). The vision was significantly improved in all eyes (p<0.05). Four eyes (12.9%) had leakage at the graft-host interface. No allograft autolysis or immunological rejection was observed. A large number of dendritic cells existed in the peripheral and central graft at 1 week postoperatively, with a mean density of 359.47±97.21 cells/mm(2) and 216.93±57.86 cells/mm(2), respectively, which significantly decreased to 93.83±31.07 cells/mm(2) and 43.65±28.43 cells/mm(2) at 2 months. Accordingly, the dosage of medication was gradually reduced during this period. At 6 months, if no dendritic cells were found in the graft, use of the topical drug was stopped. The disease recurrence rate was 9.7%. CONCLUSIONS: Modified LK, combined with immunosuppressive therapy, can effectively treat perforated Mooren's ulcer, with few complications. The use of corticosteroids and immunosuppressants guided by IVCM may reduce the disease recurrence.

Prevalence and antimicrobial susceptibilities of anaerobic bacteria isolated from perforated corneal ulcers by culture and multiplex PCR: an evaluation in cases with keratitis and endophthalmitis.

BACKGROUND: Anaerobic bacteria play an important role in eye infections; however, there is limited epidemiologic data based on the the role of these bacteria in the etiology of keratitis and endophthalmitis. The aim of this re- search is to determine the prevalence of anaerobic bacteria in perforated corneal ulcers of patients with keratitis and endophthalmitis and to evaluate their antimicrobial susceptibilities. METHODS: Corneal scrapings were taken by the ophthalmologist using sterile needles. For the isolation of anaerobic bacteria, samples were inoculated on specific media and were incubated under anaerobic conditions obtained with Anaero-Gen (Oxoid & Mitsubishi Gas Company) in anaerobic jars (Oxoid USA, Inc. Columbia, MD, USA). The molecular identification of anaerobic bacteria was performed by multiplex PCR and the susceptibilities of an- aerobic bacteria to penicillin, chloramphenicol, and clindamycin were determined with the E test (bioMerieux). RESULTS: 51 strains of anaerobic bacteria belonging to four different genuses were detected by multiplex PCR and only 46 strains were isolated by culture. All of them were found susceptible to chloramphenicol whereas penicillin resistance was found in 13.3% of P.anaerobius strains, clindamycin resistance was found in 34.8% of P.acnes and 13.3% of P. anaerobius strains. Additionnaly, one strain of P. granulosum was found resistant to clindamycin, one strain of B. fragilis and one strain of P.melaninogenica were found resistant to penicillin and clindamycin. CONCLUSIONS: Routine analyses of anaerobes in perforated corneal ulcers is inevitable and usage of appropriate molecular methods, for the detection of bacteria responsible from severe infections which might not be deter- mined by cultivation, may serve for the early decision of the appropriate treatment. Taking into account the in- creasing antimicrobial resistance of anaerobic bacteria, alternative eye specific antibiotics effective against anaer- obes are needed to achieve a successful treatment.

[Morphology and medical correction of reparative regeneration processes in corneal injury].

Analysis of current literature on morphology of wound processes in the cornea during up-to-date techniques effecting keratogenesis is performed.