Treatment Of Infectious Keratitis Research Articles

Application of Metagenomic Next-Generation Sequencing in the Diagnosis of Infectious Keratitis.

To determine the advantages of next-generation metagenomic sequencing (mNGS) technology in the diagnosis and treatment of infectious keratitis (IK). A total of 287 patients with IK admitted to the Department of Ophthalmology of Nanjing First Hospital between August 2018 and December 2022 were analyzed retrospectively, and the pathogenic causes, etiological characteristics, detection, treatment methods, and efficacy were summarized. Trauma and foreign matter were the most common causes of IK (144 patients, 50.2%). Of the 287 patients, 228 (79.4%) were diagnosed with a specific etiology, including 110 (48.2%) fungal infections, 44 (19.3%) viral infections, 42 (18.4%) mixed infections, and 30 (13.2%) bacterial infections. Filamentous fungi represented by Fusarium and Aspergillus were the most common, followed by bacteria such as Pseudomonas aeruginosa, Streptococcus pneumoniae, viruses (Herpes Simplex Virus/Varicella-Zoster Virus), and parasites. The positivity rates of secretion culture, corneal laser confocal microscopy (CM), mNGS, and pathological sections were 47.3% (133/281), 45.3% (111/245), 83.9% (104/124), and 19.3% (40/207), respectively. The positivity rate of mNGS for bacteria and viruses was higher than that of the other methods, and the positivity rate for fungi was the same as that for CM. As a result, 214 cases (74.6%) were cured, 51 cases (17.8%) improved, 8 cases (2.8%) did not heal, ocular content enucleation was performed in 14 cases (4.9%), and the overall efficacy rate was 92.3%. Trauma and foreign matter are the main causes of IK. The mNGS technology is an efficient and comprehensive detection method for viruses and bacteria, especially for mixed infections.

Quantitative evaluation of corneal irregularity and scarring after infectious keratitis using anterior segment optical coherence tomography

PurposeCorneal scars after infectious keratitis lead to insufficient transparency and irregular astigmatism, affecting visual acuity; therefore, they should be accurately evaluated to estimate visual function. This study aimed to quantitatively evaluate corneal irregularity and scarring after infectious keratitis using anterior segment optical coherence tomography (AS-OCT).MethodsThis was an observational clinical study. We included patients who had corneal scarring after treatment of infectious keratitis between 2014 and 2021 at University of Tokyo Hospital. We retrospectively examined best spectacle-corrected visual acuity (BSCVA), average keratometric power, central corneal thickness (CCT), and four components of the Fourier harmonic analysis including spherical and asymmetry components, as well as regular astigmatism and higher-order irregularity. We included anterior and posterior corneal data and compared results with those of contralateral healthy eyes. Additionally, we quantitatively evaluated the densitometry of the cornea obtained using AS-OCT.ResultsA total of 122 eyes of 61 patients were examined; male predominance was observed (n = 37), and the mean patient age was 55.3 ± 19.4 years. Comparisons with contralateral healthy eyes showed that BSCVA worsened (0.30 ± 0.83 and 0.93 ± 1.36 logMAR, respectively, P = 0.003), and CCT (531.1 ± 46.2 and 591.8 ± 132.4 μm, respectively, P < 0.001) and corneal densitometry (84.4 ± 11.8 and 111.9 ± 19.2 grayscale units, respectively, P < 0.001) increased significantly in affected eyes. The asymmetry component and higher-order irregularities that were not corrected with spectacles significantly increased (both P < 0.001), and there were no significant differences in the changes among the bacterial, fungal, herpetic, and acanthamoeba types of keratitis.ConclusionCorneal scarring persisted after treatment for infectious keratitis, and the asymmetry and irregularities of corneal astigmatism increased as visual acuity deteriorated. AS-OCT with the Fourier harmonic analysis was useful for evaluating corneal topographic changes in patients with corneal scarring after keratitis.

Antimicrobial Drug-Drug Interactions in the Treatment of Infectious Keratitis.

Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs. Using a panel of 9 ophthalmic antibiotics, 3 antifungal agents, and 2 antiacanthamoeba therapeutics, fractional inhibitory concentration testing in the standard checkerboard format was used to study 36 antibiotic-antibiotic combinations, 27 antibiotic-antifungal combinations, and 18 antibiotic-antiacanthamoeba combinations against both Staphylococcus aureus and Pseudomonas aeruginosa for synergistic, additive, neutral, or antagonistic drug-drug interactions. We demonstrate that while most combinations resulted in no change in antimicrobial efficacy of individual components, the combination of erythromycin + polyhexamethylene biguanide was found to be antagonistic toward P. aeruginosa . Conversely, 18 combinations toward S. aureus and 15 combinations toward P. aeruginosa resulted in additive or synergistic activity, including 4 with improved activity toward both species. Understanding how drug-drug interactions may affect drug efficacy is critical to selecting the appropriate combination therapy and improving clinical outcomes of this blinding disease.

A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases.

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

Changes in corneal higher-order aberrations during treatment for infectious keratitis

This study aimed to quantify the changes in corneal higher-order aberrations (HOAs) before and after treatment for infectious keratitis and verify the correlation between corneal HOAs and visual acuity. Corneal HOAs were analysed using swept-source anterior segment optical coherence tomography (AS-OCT). Ninety-eight eyes of 96 consecutive patients with infectious keratitis treated with topical eye drops were retrospectively evaluated. Corneal HOAs increased with the infection but decreased with infection resolution following antimicrobial treatment. Corneal HOAs became larger as the degree of corneal findings became more severe. The increase in HOAs of the total cornea was correlated with the decrease in visual acuity both before and after treatment (4 mm, ρ = 0.530 and 0.590; 6 mm, ρ = 0.479 and 0.567, respectively; all P < 0.0001). Furthermore, pretreatment HOA (anterior, 6 mm), pretreatment logMAR best spectacle-corrected visual acuity, and age were prognostic factors significantly associated with posttreatment visual acuity (β = 0.31, P = 0.013; β = 0.36, P < 0.0001; and β = 0.35, P = 0.0007, respectively) (adjusted R2 = 0.474). These results indicate that corneal HOAs quantified using AS-OCT can be used as an objective index to evaluate corneal optical function during the treatment of infectious keratitis.

Class-Aware Attention Network for infectious keratitis diagnosis using corneal photographs

Infectious keratitis is one of the common ophthalmic diseases and also one of the main blinding eye diseases in China, hence rapid and accurate diagnosis and treatment for infectious keratitis are urgent to prevent the progression of the disease and limit the degree of corneal injury. Unfortunately, the traditional manual diagnosis accuracy is usually unsatisfactory due to the indistinguishable visual features. In this paper, we propose a novel end-to-end fully convolutional network, named Class-Aware Attention Network (CAA-Net), for automatically diagnosing infectious keratitis (normal, viral keratitis, fungal keratitis, and bacterial keratitis) using corneal photographs. In CAA-Net, a class-aware classification module is first trained to learn class-related discriminative features using separate branches for each class. Then, the learned class-aware discriminative features are fed into the main branch and fused with other feature maps using two attention strategies to assist the final multi-class classification performance. For the experiments, we have built a new corneal photograph dataset with 1886 images from 519 patients and conducted comprehensive experiments to verify the effectiveness of our proposed method. The code is available at https://github.com/SWF-hao/CAA-Net_Pytorch.

Comparative Study of Corneal Collagen Crosslinking (CXL) in Conjunction with Antimicrobial Agents to Antimicrobial Agents Alone in the Treatment of Infectious Keratitis

Purpose: To compare the outcome of corneal collagen crosslinking (CXL) in conjunction with antimicrobial agents (AMA) to antimicrobial agents alone in the treatment of infectious keratitis. Design: Prospective comparative clinical trial in a tertiary hospital in India. Participants: 40 patients with infectious keratitis randomised into two groups of 20 patients each- Group 1 and 2. Methods: Group 1 patients underwent CXL in addition to antimicrobial therapy. The patients in Group 2 received only antimicrobial therapy. The slit-lamp characteristics of the corneal ulceration, visual acuity, time taken for healing, and complications were documented in each group. The t-test was used for statistical analysis. P values less than 0.05 were considered statistically significant. Results: The mean time taken for healing in Group 1 was 44.5±11.2 days and in Group 2 was 27.65±7.79 days. Analysis of various parameters revealed that patients undergoing CXL showed slower healing duration (p=0.00). Conclusions: Use of CXL in conjunction with AMA lowers the risk of complications, but also slows the rate of healing of ulcers.

Применение PACK-кросслинкинга при инфекционных кератитах и неэффективности местной консервативной терапии (клинические случаи)

Purpose. To present the results of PACK (Photo-Activated Chromophore for Keratitis) treatment of infectious keratitis with ineffective drug therapy using the example of clinical cases. Material and method. Under observation were 6 patients aged 28–55 years (5 men and 1 woman) with infectious keratitis (bacterial, viral-bacterial, acanthamoeba-bacterial, fungal). All of them received no effect within 5 weeks – 2.5 months. drug therapy (local and systemic) at the place of residence. All patients underwent PACK crosslinking. Results. Complete relief of the process was observed in all patients within 4–7 weeks (on average, after 39.2 days). As a result of treatment, in half of the patients (3 out of 6) visual acuity increased to 0.4–0.8, in 3 patients it did not change significantly after treatment and corresponded to light perception with the correct projection of light – 0.01–0.02, since the inflammatory process ended with severe corneal clouding. Conclusion. Corneal PACK crosslinking appears to be an effective and promising technique for the treatment of infectious keratitis resistant to ongoing drug therapy. In cases of the outcome of the infectious process with the formation of persistent and pronounced clouding (thorn) in such patients in the «cold» period after the arrest of the infectious process, keratoplasty with an optical purpose can be performed. Key words: infectious keratitis, drug therapy failure, PACK crosslinking, optic keratoplasty

Trends in research on corneal cross linking from 2001 to 2020: a bibliometric analysis

ABSTRACT Clinical relevance The research status and hotspots in the field of corneal cross linking (CXL) can benefit clinicians, researchers and the general public. Background The purpose of this study was to map the publishing trend on CXL research and explore the research hotspots. Methods A bibliometric analysis was performed using the Web of Science Core Collection to investigate the publishing trend on CXL research. VOSviewer was used to build the knowledge map to visualise the number of annual publications, distribution of countries and institutions, international cooperation, author productivity, source journals and research hotspots in the field of CXL. Results A total of 2061 peer-reviewed articles on CXL research were collected from 2001 to 2020, and the annual research production increased over time. The United States was the country with the largest number of published articles, and the University of Zurich was the most active institution. Hafezi F published the largest number of articles on CXL, while Cornea was the journal with the largest number of studies on CXL. The most frequently cited references mainly focus on CXL in the treatment of keratoconus. The keywords were divided in 5 categories: 1) CXL mechanism, 2) ectasia diseases and refractive surgery, 3) corneal biomechanics, 4) efficacy evaluation, 5) treatment of infectious keratitis. Conclusion The quantity and quality of articles on CXL were evaluated using bibliometric techniques by extracting the data from the Web of Science Core Collection. The research hotspots could provide insights on CXL research, providing valuable information for clinicians to perform research in this field and find potential partners.

Amniotic Membrane Transplantation for Persistent Epithelial Defects and Ulceration due to Pseudomonas Keratitis in a Rabbit Model.

PurposeThe use of amniotic membrane has been suggested in the treatment of infectious keratitis for its intrinsic anti-infective properties probably mediated by its anti-inflammatory effects. The aim of this study was to investigate the effect of amniotic membrane transplantation (AMT) along with ciprofloxacin to cure the primary stages of Pseudomonas keratitis.MethodsIn total, 28 rabbits were selected and divided in four groups as follows: group 1 as control, group 2 with amniotic membrane, group 3 with ciprofloxacin, and group 4 with amniotic membrane combined with ciprofloxacin. About 0.05 cc suspension of Pseudomonas aeruginosa, 27853 ATCC was injected into corneal stroma.ResultsThe results showed groups of AMT, AMT + ciprofloxacin, and ciprofloxacin had 0% perforation while the control group had 85.6%. Average infiltration of 5.5 mm was observed in ciprofloxacin group, 5 mm in AMT + ciprofloxacin group, 24 mm in AMT group, and finally 23.75 mm for control. Amniotic membrane showed to be effective in prevention of cornea perforation as well as remission of Pseudomonas keratitis. There was no significant difference between ciprofloxacin groups in comparison with ciprofloxacin + AMT group. However, regarding the anti-inflammatory effect, the process of improvement of inflammation in ciprofloxacin + AMT group was faster.Conclusion Transplantation of amniotic membrane in the primary stages of Pseudomonas keratitis treatment remarkably prevents the disease and it can be used to control its process.

Super aggregated amphotericin B with a thermoreversible in situ gelling ophthalmic system for amoebic keratitis treatment

Acanthamoeba spp. are the causative agents of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK). Amphotericin B - deoxycholate (AB) is used in the treatment of infectious keratitis, however, its topical administration has side effects as blepharitis, iritis, and painful instillation. In this context, the preheating of AB can decrease its toxicity by the formation of super aggregates (hAB). hAB associated with a thermoreversible in situ gelling ophthalmic system is a promising option due to the latter biocompatibility, low toxicity, and high residence time on the ocular surface. Our objective was to develop a topical ocular formulation of hAB for the treatment of AK. After heating at 70°C for 20 min, hAB was incorporated into a thermoreversible gelling system. The amebicidal activity of AB and hAB was evaluated against trophozoites and cysts of A. castellanii (ATCC 50492) and a regional clinical isolate (IC01). The results showed that the preheating of AB did not change the pharmacological action of the drug, with the amebicidal effect of AB and hAB under trophozoites and cysts of Acanthamoeba spp. The thermoreversible system remained stable, allowing the increase of drug retention time. For assessment of cytotoxicity, HUVEC (ATCC® CRL-1730) cells were challenged with AB and hAB for 48h. Cell viability was assessed, and hAB did not show cytotoxicity for HUVEC cells. As far as we know this was the first study that showed the preheated AB associated with a thermoreversible in situ gelling ophthalmic system as a promising system for topical ocular topical administration of hAB for AK therapy.

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.

Corneal Microneedles: Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis (Adv. Healthcare Mater. 11/2021)

Corneal Microneedles: Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis (Adv. Healthcare Mater. 11/2021)

Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis.

Infectious keratitis is mainly treated with topical antibiotics. To achieve and maintain the required therapeutic concentration in the cornea where the tear fluid continuously rinses the surface, the antibiotics must be frequently applied, even while the patient is sleeping, and oral medication is sometimes required. However, the inevitably poor compliance and avascular nature of the cornea decrease drug bioavailability. In this study, a single microneedle (MN) is injected into the cornea to substitute for the repeated application of eyedrops in the treatment of infectious keratitis. After comparing the mechanical integrity and drug release profiles of three different drug-tips, the drug-tip with the "high" drug concentration that releases 12.5ng drug within 3 days is applied to a cornea to evaluate the transferability and in vivo drug release. In the treatment of infectious keratitis with repeated application of eyedrops for six consecutive days, a single MN injection is substituted for the initial 3 days of eyedrop applications. The progression remains similarly attenuated after 3 days without eyedrops, and comparable efficacy is achieved on day 6 when combined with delayed eyedrop treatment from day 3. Thus, the single administration of a biodegradable MN can substitute for the repeated application of eyedrops in the treatment of infectious keratitis.

Alternative indications for corneal crosslinking.

Corneal crosslinking (CXL) is the current mainstay treatment for progressive keratoconus. In the past 15 years, a variety of other indications have been tested. A systematic review was conducted to examine these alternative indications for CXL. In total, 143 papers on crosslinking as a treatment for infectious keratitis, bullous keratopathy, pellucid marginal degeneration, and postlaser in situ keratomileusis (LASIK) ectasia and as a way to improve vision either on its own or in combination with other interventions were included. Post-LASIK ectasia is a definite indication for crosslinking. Surprisingly, only limited research has been performed on pellucid marginal degeneration, with no randomized trials available to date. Other interesting applications are the combined use of refractive lasers and crosslinking for suspicious or ectatic corneas and crosslinking as a standalone intervention for minor refractive errors. CXL might offer a solution for refractory bacterial keratitis. In bullous keratopathy, it seems to offer only a transient benefit.

Treatment of Severe Infectious Keratitis With Scleral Contact Lenses as a Reservoir of Moxifloxacin 0.5.

To report the outcomes of using scleral contact lenses as antibiotic reservoirs as a therapeutic approach in a case series of severe infectious keratitis and to discuss the clinical potential. This was a prospective consecutive case series study of 12 eyes treated for infectious keratitis at the "Conde de Valenciana" Institute of Ophthalmology. A scleral lens (SL) filled with 0.5% moxifloxacin was used as a reservoir and replaced every 24 hours until epithelization was complete or the culture report and/or antibiogram demonstrated either a microorganism not susceptible to or resistant to moxifloxacin. The study included 12 eyes of 12 patients (7 women; 58.33%; average age of 63 ± 20.11 years). All patients completed at least 1 month of follow-up. Patients had a diagnosis of infectious keratitis, and the SL was fitted on initial consultation. Of the 12 eyes, 7 had culture-positive bacterial infection, 2 eyes were mycotic, and 3 eyes had no culture growth. In 3 eyes, SL was discontinued because of the lack of response (one eye) and to the presence of mycotic infection (2 eyes). All infections resolved favorably at the final follow-up. The use of SLs could be an alternative for antibiotic impregnation and treatment of infectious keratitis. No complications or side effects were observed related to the use of the scleral contact lens as a reservoir for the antibiotic. This treatment modality could offer a comfortable treatment for the patient, ensuring good impregnation and maintenance of antibiotic concentrations during the 24-hour wear periods.

A summary of China's 70 years of development in diagnosis and treatment targeting corneal diseases

Since the founding of the People's Republic of China, the diagnosis and treatment technology of corneal diseases has developed rapidly. In the field of infectious keratopathy, China was the first country that discovered chlamydia trachomatis in the world, which promoted the study on the pathogenesis as well as the diagnosis and treatment of infectious keratitis, especially fungal keratitis. In the aspect of surgical technology, we have learned from other countries and innovated different types of transplantation surgeries suitable for patients with corneal diseases in China. Regarding the construction of eye banks, the cornea donation process and the operation techniques have been developed and standardized. In addition, to improve the cornea disease-related inspection level, new equipment such as specular microscopy and confocal microscopy has been introduced. These efforts have decreased corneal diseases from the first blinding eye disease to the second in our country. In the past 70 years, China's diagnosis and treatment technology in corneal diseases has achieved remarkable progresses, but there are still many shortcomings. Standing on the shoulders of the older generations of ophthalmologists, we should continue to serve the patients with corneal diseases wholeheartedly. We would like to send congratulations on the 70th anniversary of Chinese Journal of Ophthalmology with this article. ( Chin J Ophthalmol, 2020, 56: 401-408).

Les effets du cross-linking cornéen sur la mesure de pression intra-oculaire dans le kératocône

Cross-linking (CXL) is a technique whose design aims to achieve a specific goal: to harden the corneal tissue of eyes with a progressive form of keratoconus. Other indications are being investigated, such as treatment of infectious keratitis and prevention of corneal ectasia post corneal ablative refractive surgery. Hardening the cornea means changing its biomechanical properties. The existence of true corneal hardening after CXL would inevitably result in an increase in measured intraocular pressure (IOP). This would have a considerable impact in the screening and follow-up of glaucoma patients who have undergone cross-linking because of the central role of IOP measurement in glaucomatous pathology.

Contact Lenses and Infectious Keratitis

We review the evolution of contact lenses, risk factors for contact lens-related infectious keratitis, and updates on management. Infectious keratitis is still a devastating complication of contact lens use, with improper lens hygiene and use as significant risk factors. Cosmetic contact lenses have become popular among the younger generations. They can be obtained online without a doctor’s prescription or supervision, leading to an increased risk of serious infection. Topical antibiotics remain the best treatment for bacterial keratitis, but resistance to fourth-generation fluoroquinolones has increased. Fungal ulcers fare worse than bacterial ulcers, with no new commercially available topical treatments since topical natamycin. Despite the well-established link between water exposure of contact lenses and development of Acanthamoeba keratitis, patients still regularly expose their lenses to tap water. Corneal cross-linking, new methods for antimicrobial drug delivery, and novel antimicrobial targets represent the next frontiers in the treatment of infectious keratitis. Contact lens-related infectious keratitis remains a serious cause of ocular morbidity, with the rates of atypical causative organisms (Acanthamoeba and fungus) on the rise. Strategies for risk reduction include prevention through patient education; collaboration with industry to develop novel antimicrobials, lens materials, and care system products; and reporting of infections and illegal sale of contact lenses to regulatory agencies such as the United States Food and Drug Administration (FDA) and the Federal Trade Commission (FTC).

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.