Treatment Of Infectious Keratitis Research Articles

Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis

The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also their components such as lipopolysaccharide (LPS) of Gram-negative bacteria contribute to the development of inflammation and subsequent corneal damage in infectious keratitis. We describe the important role played by corneal stromal fibroblasts (activated keratocytes) as sentinel cells, immune modulators, and effector cells in infectious keratitis. Corneal fibroblasts sense bacterial infection through Toll-like receptor (TLR)–mediated detection of a complex of LPS with soluble cluster of differentiation 14 (CD14) and LPS binding protein present in tear fluid. The cells then initiate innate immune responses including the expression of chemokines and adhesion molecules that promote the recruitment of inflammatory cells necessary for elimination of the infecting bacteria. Infiltrated neutrophils are activated by corneal stromal collagen and release mediators that stimulate the production of pro–matrix metalloproteinases by corneal fibroblasts. Elastase produced by Pseudomonas aeruginosa (P. aeruginosa) activates these released metalloproteinases, resulting in the degradation of stromal collagen. The modulation of corneal fibroblast activation and of the interaction of these cells with inflammatory cells and bacteria is thus important to minimize corneal scarring during treatment of infectious keratitis. Pharmacological agents that are able to restrain such activities of corneal fibroblasts without allowing bacterial growth represent a potential novel treatment option for prevention of excessive scarring and tissue destruction in the cornea.

Fertőzéses keratitisek diagnosztikája és kezelése

We summarize up-to-date diagnostic and treatment of infectious keratitis using literature data and some clinical examples. In the clinical practice, most commonly bacterial, herpetic, mycotic and acanthamoeba keratitis occur. Beside slitlamp examination, for diagnostic purpose, we analyse corneal sensitivity, perform in vivo confocal microscopy, polymerase-chain-reaction (PCR), in vitro culture and histological examination of the corneal sample. As conservative treatment we use primarily topical moxifloxacin or cephasolin with fortified tobramycin or gentamycin in bacterial, topical antiviral gel (in some cases in combination with systemic antiviral treatment) in part in combination with topical corticosteroids in herpetic, voriconasole or amphotericin-B in mycotic, and topical-triple-therapy (diamidine, biguanid and antibiotics) in acanthamoeba keratitis. In case of early diagnosis and initiation of topical therapy, most cases of infectious keratitis recover successfully. However, beside conservative treatment, penetrating keratoplasty, amniotic membrane transplantation and crosslinking therapy may be necessary. Crosslinking is solely contraindicated in herpetic keratitis. Orv Hetil. 2017; 158(31): 1203-1212.

Corneal collagen cross-linking in the treatment of infectious keratitis and corneal ulcers

In recent years, collagen cross-linking (CXL) of the cornea has acquired a new usage - in the treatment of infectious keratitis and corneal ulcers. This review was aimed at compiling the previously published data and assessing the effectiveness of the method.

Corneal Collagen Cross-linking in Infective Keratitis

ABSTRACT Purpose of review To summarize the current understanding of effects of cross-linking (CXL) in infective keratitis based on available evidence. Method of literature search A PubMed search was conducted with combinations not limited to the following search terms: corneal collagen CXL, riboflavin, ultraviolet A, keratoconus, microbial keratitis, fungal keratitis, bacterial keratitis, Acantha-moeba keratitis. A review of the search results was performed and relevant articles to the topic were included. Summary Most of the published literature showed promising results in treatment of infectious keratitis by corneal collagen CXL using photoactivated riboflavin as an adjuvant therapy but with questionable efficacy in deep keratitis due to slow-growing organisms. How to cite this article Ummar S, Farrag AN. Corneal Collagen Cross-linking in Infective Keratitis. Int J Kerat Ect Cor Dis 2016;5(1):13-16.

The Role of Ultraviolet Radiation in the Ocular System of Mammals

With decreasing levels of ozone in the atmosphere, we are being exposed to higher levels of ultraviolet radiation (UVR) than ever before. UVR carries higher energy than visible light, and its effects on tissues include DNA damage, gene mutations, immunosuppression, oxidative stress and inflammatory responses. In the eye, UVR is strongly associated with the development of basal and squamous cell carcinoma of the eyelid, pterygium, photokeratitis, climatic droplet keratopathy, ocular surface squamous neoplasia, cataracts, and uveal melanoma, and is weakly associated with age-related macular degeneration. Despite overwhelming evidence regarding the deleterious effects on UVR, public health measures to encourage UV protection of the eyes is generally lacking. Options for photoprotection include sunglasses, wide brim hats, windshields, plastic films for side windows in cars, UV blocking contact lenses, and following the UV Index report daily. The American National Standards Institute currently has regulations regarding properties of UV blocking sunglasses; however, compliance in the US is not mandatory. On the other hand, UVR does have therapeutic applications in the eye, particularly, riboflavin activated by ultraviolet A light (UVA) radiation is used clinically to slow the progression of keratoconus, post-LASIK keratectasia, and bullous keratopathy by crosslinking corneal collagen fibers. Additionally, riboflavin activated by UVA has been shown to have antibacterial, antiviral, and antiparasitic effects. This is clinically relevant in the treatment of infectious keratitis. Finally, exposure to low levels of light in the UV spectrum has been found to regulate the growth of the eye and lack of adequate exposure may increase the risk of development and progression of myopia.

Rapid and sensitive diagnosis of fungal keratitis with direct PCR without template DNA extraction

This study was aimed at developing a direct PCR assay without template DNA extraction for the rapid and sensitive diagnosis of infectious keratitis. Eighty corneal scrapings from 67 consecutive patients with clinically suspected infectious keratitis were analysed prospectively. Direct PCR was performed with all scrapings, with specific primers for fungi, bacteria, herpes simplex virus-1 (HSV-1) and Acanthamoeba simultaneously. The results were compared with those obtained from culture, smear, and confocal microscopy. Discrepant results were resolved according to the therapeutic effects of the corresponding antimicrobial drugs. The lowest detection limit of direct PCR was ten copies of each pathogen. Sixty-six scrapings yielded positive results with direct PCR, giving a total positive detection rate of 82.5% (66/80). For 34 patients with high suspicion of fungal keratitis, the positive detection rate of direct PCR was 84.8% (39/46). This rate increased to 91.2% (31/34) when repeated scrapings were excluded, and was significantly higher than the rates obtained with culture (35.3%, 12/34) and smear (64.7%, 22/34) (p <0.001), and was also higher than the rate obtained with confocal microscopy (74.1%, 20/27). The sensitivities for the diagnosis of infectious keratitis with direct PCR and culture were 98.0% and 47.1% (p <0.001), whereas the specificities were 81.8% and 100%, respectively. The time required to complete the entire direct PCR procedure was only 3 h. The direct PCR assay is a rapid diagnostic technique with high sensitivity and specificity for infectious keratitis, and it is expected to have an impact on the diagnosis and treatment of infectious keratitis in the future.

Corneal collagen crosslinking in the treatment of infectious keratitis

To investigate the feasibility and clinical efficacy of corneal collagen crosslinking (CXL) for the treatment of infectious keratitis. Noncomparative interventional case series.19 patients with infectious keratitis admitted to our hospital between November 2011 and January 2012 were recruited into this study, CXL was performed when medications combined proved poor therapeutic effects. Postoperatively, the graft status, graft clarity, the visual prognosis and postoperative complications were recorded. In 15 cases, there was improvement in symptoms one week after operation.3 cases remained stable, while 1 case reported deteriorated function at the same time.One month after operation, Corneal melting was arrested and complete epithelialization was achieved in 13 cases, 5 cases experienced significant improvement and 1 patient experienced corneal ulcer perforation.2 month after surgery, patients with healed corneal ulcer increased to 17 cases, and 2 cases experienced corneal ulcer perforation. Those 17 cases with healed corneal ulcer were followed up for 6 months, 15 cases had significant improvement in best-corrected visual acuity, 2 cases had no significant change, and no relapse was observed in those 17 cases. Our experience based on the above and other cases suggest that CXL could be an effective tool in battling difficult cases of infectious keratitis. This treatment could present many advantages but will need further investigation both by in vitro and in vivo studies.

Impending corneal perforation after collagen cross-linking for herpetic keratitis

Collagen crosslinking (CXL) has been proposed as a treatment for infectious keratitis. Given the insurgence of antibiotic-resistant microorganisms and frequent toxicity of topical medications, CXL may be a potential treatment for corneal infections. However, corneal infection is itself a possible complication of this treatment. We describe a case of severe corneal thinning and melting in a woman who had a CXL procedure as a treatment for herpetic keratitis.

Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis of reported cases

BackgroundCollagen cross linking (CXL) of the cornea has been developed recently as a new treatment for multidrug-resistant infectious keratitis. The aim of this study is to summarize the previously published data and evaluate the effectiveness of this treatment.ResultsThe search identified 12 articles. The number of eyes was 104. The infectious keratitis was associated with bacteria in 58 eyes (57f%): Gram-positive bacteria in 44 (43%; 4 of which were infected with Mycobacterium (3.6%)) and Gram-negative bacteria in 14 eyes (13%), fungus in 13 eyes (12%), and Acanthamoeba in 7 eyes (7%). In 26 eyes (25%), the microbiological culture was negative or not performed. The mean time of re-epithelization after CXL was 20.7±28.1 days (minimum of 3, maximum of 145). Sixteen eyes underwent deep or lamellar keratoplasty. The pooled analysis suggested that CXL has a favorable effect on the block of corneal melting in 85% (95%; CI 0.77, 0.91) of eyes.ConclusionAlthough randomized controlled trials are needed, the available evidence supports the use of CXL in the treatment of infectious keratitis.

The role of Confocal Microscopy in evaluation and treatment of infectious keratitis

AbstractPurpose To evaluate the role of in vivo confocal microscopy (IVCM) in the diagnosis and treatment of infectious keratitis.Methods 24 patients with keratitis were examined by slit‐lamp biomicroscopy and IVCM (HRT). All IVCM examinations were assessed for inflammatory activity and potential etiology. After obtaining baseline cultures, patients were treated as bacterial (10), viral (5), fungal (8) or Acanthamoeba (1) related keratitis based on clinical findings and IVCM.Results Primary outcome was clinical improvement, secondary outcome was correlation between IVCM findings and final culture. In 23 cases (9 bacterial, 5 viral, 8 fungal and 1 Acanthamoeba) clnical improvement was observed within 21 days whereas 1 patient worsened. In bacterial suspected group cultures were positive in 7 cases (70%), in viral none of the cultures were positive. Despite typical clinical image and IVCM findings and clinical improvement on adequate medication in fungal and Acanthamoeba suspected groups cultures remained negative.Conclusion Our study suggests that IVCM along with clinical evaluation can be a useful tool in early diagnosis and guided treatment of patients with infectious keratitis, until definitive culture results are available. However, a prospective clinical study is recommended to further study the role of IVCM in infectious keratitis.

Profile of sight-threatening infectious keratitis: a prospective study

To prospectively study patients presenting with sight-threatening corneal ulcers with a view to identify the predisposing factors, causative organisms, clinical signs and treatment outcomes. Prospectively, over 3-year period, all cases with serious infective keratitis presenting to Queens Medical Hospital in Nottingham, UK, were recruited. Detailed information on the aetiology, culture results, signs & symptoms, the treatment given and the patient's response was collected and statistically analysed. One hundred and forty-three eyes of 129 patients were enrolled. Thirty-one patients were managed as out-patients, and 98 were treated as in-patients. The mean duration of admission was 9 ± 13 days but was significantly higher in older patients and in Acanthamoeba keratitis cases. The important risk factors were ocular surface disease (32%), contact lens wear (26%) and previous ocular surgery (20%). Old age, deep infiltration, steroid use and poor initial vision were risk factors for prolonged course of treatment in bacterial keratitis. Corneal scrapings were done in 89% of the cases, but positive results were obtained only in 41.7%. Staphylococcus aureus was the most common isolated bacteria (18.8%). Acanthamoeba and Pseudomonas aeruginosa were the second and third common causative organisms (16.6% and 15%, respectively). Overall, 8.3% needed corneal grafting, which survived in 83.3% and eradicated infection in 100%. Microbial keratitis is an important cause of ocular morbidity. Previous ocular disease is an important predisposing factor. Old age, steroid use and poor presenting visual acuity are important prognostic indicators. Corneal grafting is an effective option for managing recalcitrant corneal infections.

Indução de ligações covalentes do colágeno (cross-linking) da córnea para estabilização da ectasia progressiva

ABSTRACT The induction of corneal collagen cross-linking by ultraviolet radiation (UV) over a substract of riboflavin was popularized and dubbed as CXL (corneal cross-linking). In 2003, this technique was introduced in the therapeutic arsenal for patients with keratoconus, aiming to halt the progression of the disease. The procedure would enhance biomechanical and biochemical corneal stability by the formation of new covalents bonds in the amino-termial sites of the collagen molecule of the anterior stroma. Such induction depended on the hydrogen singlets free radicals generated by the riboflavin photosensibilization by UV-A. CXL is indicated in corneal thinning and progressive ectasias, as it happens in keratoconus, post-LASIK ectasia and pellucid marginal degeneration. Other anecdotic indications are described in the literature such as treatment of infectious keratitis, control of bullous keratopathy and corneal melting; however, they will not be discussed in this review. The CXL for the treatment of progressive corneal ectasia is a procedure that does not involve sophisticated equipments. It is safe (low odds of complications), not expensive and with high efficacy (halting the progression of ectasia). The great majority of treated patients are young adults. There are some contraindications for this procedure such as minimum corneal thickness of 400 µm, which is the most feared. The classic technique was described in 1995 by German researchers and variations of this technique still under evaluation. The CXL is a recent procedure and, besides some favorable results, a long-term follow up (more than 5 years) is needed, to evaluate collateral side effects and potential complications.

Corneal collagen crosslinking in the treatment of infectious keratitis

PurposeTo report the use of corneal collagen crosslinking in the treatment of infective keratitis not responding to antimicrobial therapy.MethodsTwo retrospective case reports of infective keratitis treated with corneal collagen crosslinking.ResultsIn both cases, corneal collagen crosslinking caused a rapid resolution of the infective keratitis, leaving residual stromal scarring. Due to the density of scarring, one case required subsequent penetrating keratoplasty for visual rehabilitation.ConclusionCorneal collagen crosslinking is a promising new technique for the management of infective keratitis not responding to antimicrobial therapy. Further elucidation of its safety and role in management of infectious keratitis is needed by way of future studies.

In Vitro Evaluation of the Antibiotic Activity of Combinations of Ophthalmic Drugs Against Common Equine Ocular Pathogens

A subpalpebral lavage catheter is commonly used to administer medications in the treatment of infectious keratitis in horses. Drugs may mix in the subpalpebral lavage catheter, potentially affecting antimicrobial efficacy. The objective of this study was to determine the in vitro antimicrobial efficacy of combinations of commonly used ophthalmic preparations. An agar gel diffusion bioassay was used to determine the antibiotic activity of a number of antimicrobial, antifungal, mydriatic, and antiproteinase drug combinations. Drug mixtures were allowed to sit in a syringe at ambient temperatures and room lighting, for 1 (T1) and 6 hours (T2). The antibacterial efficacy was determined by measuring the zone of inhibition around wells containing the drug combinations after overnight incubation at 37°C and comparing them with the zone of inhibition around the antimicrobial alone. Combinations were tested against Pseudomonas aeruginosa and Streptococcus zooepidemicus. There was no significant decrease in the zone of inhibition, compared with controls, for the majority of combinations tested. Significantly smaller zones of inhibition were identified for the following combinations: (1) tobramycin, cefazolin, natamycin, and serum (T1) and (2) tobramycin, cefazolin, natamycin, serum, and atropine (T1) compared with tobramycin alone; (3) ciprofloxacin, cefazolin, natamycin (T1) compared with ciprofloxacin alone; (4) triple antibiotic ophthalmic solution (TAB) and natamycin (T6); (5) TAB, natamycin, and serum (T6); and (6) TAB, natamycin, serum, and atropine (T6) compared with TAB alone. Admixture does not affect in vitro antibacterial efficacy for the majority of ophthalmic preparations, although efficacy of TAB may be decreased compared with the drug alone.

Treatment of infectious keratitis with keratoplasty

目的 评价感染性角膜炎角膜移植治疗的临床效果.方法 采用深板层或穿透性角膜移植治疗真菌性角膜溃疡97例(97眼),病毒性伯膜炎21例(21眼),棘阿米巴性角膜炎3例(3眼),共121例(121眼).临床观察2～20月.结果 119眼角膜植片存活,治愈率98.35%;2例复发,复发率1.65%.结论 对药物治疗无效的感染性角膜炎及时行治疗性角膜移植术,是控制感染,挽救眼球,甚至恢复有用视力的有效方法。

Antimicrobial Efficacy of Riboflavin/UVA Combination (365 nm) In Vitro for Bacterial and Fungal Isolates: A Potential New Treatment for Infectious Keratitis

To demonstrate the antimicrobial properties of riboflavin/UVA (365 nm) against common pathogens. One group of bacteria (Pseudomonas aeruginosa [PA], Staphylococcus aureus [SA], and Staphylococcus epidermidis [SE]) was tested by using Kirby-Bauer discs with (1) empty disc (Control - C); (2) riboflavin 0.1% (B2); (3) riboflavin 0.1% previously activated by UVA (B2'); (4) UVA alone (UVA); (5) group 2+additional UVA exposure (UVA+B2); and (6) group 3+additional UVA exposure (UVA+B2'). In addition, another group of microbes was tested with the same approach: methicillin-resistant S. aureus (MRSA), multidrug-resistant P. aeruginosa (MDRPA), drug-resistant Streptococcus pneumoniae (DRSP), and Candida albicans (CA). The mean growth inhibition zone (GIZ) in square millimeters was measured around the discs. The mean standard deviation (MSD) was calculated to be 3.65 when alpha = 0.01. A mean deviation (MD) > MSD indicates a significant difference. In the first group, the GIZ was significantly greater after UVA (MD = 14.30), UVA+B2 (MD = 39.61), and UVA+B2' (MD = 40.45) when compared with C, B2, and B2'. UVA alone was less effective than UVA+B2 (MD = 25.31) and UVA+B2' (MD = 26.15). The second group demonstrated increased GIZ in UVA (MD = 6.98), UVA+B2 (MD = 17.80), and UVA+B2' (MD = 21.15) when compared with C, B2, and B2'. UVA alone was less effective against the second group of bacteria than was UVA+B2 (MD = 10.82) and UVA+B2' (MD = 14.17). CA did not show any GIZ after treatment. Riboflavin/UVA was effective against SA, SE, PA, MRSA, MDRPA, and DRSP, but was ineffective on CA and has the potential for use in treatment of microbial keratitis in the future.