Sterile Keratitis Research Articles

Outcomes of pediatric sterile keratitis posthypotonic collagen cross-linking

Abstract: In this case series, we will describe sterile keratitis in the early postoperative period after hypotonic collagen cross-linking (CXL) in two pediatric cases. This is a retrospective case series of two eyes of two children who developed inflammatory keratitis with central corneal haze after uneventful epithelial-off hypotonic CXL. After ensuring microbiological sterility, appropriate treatment with topical steroids and lubricants was started. There was complete resolution of corneal infiltrates with minimal scarring. Both patients regained almost the preoperative best-corrected visual acuity of 20/80 and 20/60, respectively.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3weeks off regimen. Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52years; range, 11-87years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6months (median, 5months; range, 1-36months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Innate Immune System Activation, Inflammation and Corneal Wound Healing.

Corneal wounds resulting from injury, surgeries, or other intrusions not only cause pain, but also can predispose an individual to infection. While some inflammation may be beneficial to protect against microbial infection of wounds, the inflammatory process, if excessive, may delay corneal wound healing. An examination of the literature on the effect of inflammation on corneal wound healing suggests that manipulations that result in reductions in severe or chronic inflammation lead to better outcomes in terms of corneal clarity, thickness, and healing. However, some acute inflammation is necessary to allow efficient bacterial and fungal clearance and prevent corneal infection. This inflammation can be triggered by microbial components that activate the innate immune system through toll-like receptor (TLR) pathways. In particular, TLR2 and TLR4 activation leads to pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation. Similarly, endogenous molecules released from disrupted cells, known as damage-associated molecular patterns (DAMPs), can also activate TLR2, TLR4 and NFκB, with the resultant inflammation worsening the outcome of corneal wound healing. In sterile keratitis without infection, inflammation can occur though TLRs to impact corneal wound healing and reduce corneal transparency. This review demonstrates the need for acute inflammation to prevent pathogenic infiltration, while supporting the idea that a reduction in chronic and/or excessive inflammation will allow for improved wound healing.

Severe marginal sterile keratitis in a patient with staphylococcal endophthalmitis after phacoemulsification

Postoperative endophthalmitis is sight-threatening, severe inflammation in posterior vitreous cavity and anterior chamber. Marginal keratitis with infiltrates or ulcers following endophthalmitis can be infectious or sterile, but the etiologies related to intraocular infection have rarely been reported. Here we present an unusual case of severe marginal keratitis with sterile infiltrates concomitant with staphylococcal endophthalmitis after phacoemulsification. Creamy white ring infiltrates at the corneolimbal junction was found with severe vitritis. With antibiotics treatment, endophthalmitis improved while the corneal infiltrates progressed. After corneal specimens yielded negative results, the corneal infiltrates improved under proper topical corticosteroid without marked sequelae. In conclusion, noninfectious, immune-related marginal sterile keratitis may develop in patients with staphylococcal endophthalmitis after phacoemulsification.

Efficacy and safety of accelerated corneal collagen cross-linking in patients with keratoconus

AIM: To study the efficacy and safety of accelerated collagen cross-linking in keratoconus. METHODS: Medical records of keratoconic corneas underwent accelerated collagen cross-linking at King Chulalongkorn Memorial Hospital, Thailand between April 2015 and August 2018 were reviewed. Preoperative and postoperative data at 1y of visual acuity, auto-refraction, corneal topography, higher-order aberrations (HOA), topometric indices and corneal densitometry were evaluated. Age of 24-30 (mean age 23.43±7.26)y, maximum keratometric value (Kmax) of 55 D, and baseline best corrected visual acuity (BCVA) of 20/40 (or 0.3 in LogMAR unit) were used as cut-off values to highlight the cross-linking effects. The effect of age, preoperative Kmax and BCVA were analyzed. The association between the change of corneal densitometry and other factors including preoperative Kmax, Kmean, manifest refraction spherical equivalent (MRSE), visual acuity, thinnest pachymetry, the change in Kmax, and the change of those parameters were also analyzed. P<0.05 was considered statistically significant. RESULTS: One hundred and fifty-five patients (185 eyes) were included. Male to female ratio was 3:31. According to Amsler-Krumeich classification, stage 1 and 2 were dominant (37.84% and 35.14% respectively). At 1y, mean LogMAR uncorrected visual acuity (UCVA) improved by 0.1 (P<0.05). The number of eyes of which postoperative BCVA improved more than 0.2 LogMAR was higher in the worse baseline BCVA group (preoperative BCVA ≥0.3) compared to the better baseline BCVA group (preoperative BCVA <0.3) (78.26% vs 21.74%, P<0.05). Mean Kmax decreased from baseline by 2.36 diopters (D) (P<0.05). Seventy-three percent of the eyes of which Kmax reduced more than 2.0 D had preoperative Kmax ≥55 D. Q-value showed less prolate by 0.06 (P<0.05). Corneal HOA at 6 mm from corneal apex decreased by 0.40 (P<0.05). Corneal densitometry at 0-6 mm zone increased at 1mo and persisted 1y postoperatively (P<0.05). The relationship of the increase in densitometric value and the decrease of thinnest pachymetry at 1y were in linear fashion. Index of surface variance, index of vertical asymmetry, keratoconus index, index of height decentration decreased at 1y (P<0.05). Success rate at 1y was 90.24%. Postoperative corneal haze was found 11.35%, 30.27%, 15.67%, 10.27% and 2.16% at 1wk, 1, 3, 6mo and 1y respectively. No eyes developed corneal edema. There was one case of sterile keratitis. CONCLUSION: Accelerated collagen cross-linking in keratoconus was effective to flatten, reshape the cornea, improved visual acuity, HOA and topometric indices. Great Kmax reduction was found in advanced keratoconus. The magnitude of Kmax reduction is also greatest among previous reports.

Clinical Outcomes of Mini-scleral Contact Lenses in Eyes with Keratoconus

Purpose: To analyze the clinical results of fitting mini-scleral contact lenses prescribed for vision correction in eyes with keratoconus, and the parameters of eyes related to the base curve radius (BCR) of the final prescribed lenses.Methods: From January 2016 to March 2021, 24 patients (44 eyes) who used mini-scleral lenses for more than 3 months due to keratoconus were enrolled. The keratoconus stage before prescription, degree of corrected visual acuity improvement, follow-up period, and complications and causes of failure to maintain the lenses were analyzed. The correlations between the BCR of the final prescribed lenses and the morphological factors of the eyes were analyzed.Results: The average Amsler–Krumeich keratoconus stage before wearing a lens was 2.2 ± 0.8 and 90.9% of patients had a corrected visual acuity improvement exceeding 2 lines. Excluding four eyes in two patients (9.9%) who gave up wearing mini-scleral lenses, the average duration of wearing lenses was 23.6 ± 17.8 months, and the average daily wearing time was 8.79 ± 3.14 hours. Complications were conjunctival injection in five eyes (three patients) and sterile keratitis and superficial punctate keratitis in one eye, respectively. The causes of failure to maintain the mini-scleral lens were injection in two eyes (one patient) and handling difficulty in two eyes (one patient), and they gave up after an average of 6 months. Only the radii of the anterior and posterior corneal best fit sphere before wearing the lens were found to have a significant positive correlation with the BCR of the finally prescribed lenses (p < 0.001).Conclusions: Mini-scleral lenses provide relatively good vision improvement without serious complications in patients at various stages of keratoconus, and the BCR of the finally prescribed lens had a good correlation with the anterior and posterior corneal best fit sphere.

Toll-like receptor gene polymorphisms in patients with keratitis

ObjectiveTo investigate differences in SNPs in TLR genes between people who had keratitis and controls in an Indian population. Methods145 cases of keratitis and 189 matched controls were recruited. DNA was extracted from peripheral blood. Single nucleotide polymorphisms (SNP) in TLR2 (n = 6), TLR4 (n = 15), TLR5 (n = 13) and TLR9 (n = 10) were analysed. The risk of developing keratitis was assessed based on allele, genotype and haplotype associations. ResultsFor all cases of keratitis, the TLR4 SNP rs4986791 TC genotype frequency was significantly higher in cases (p = 0.006, OR = 1.96, 95 % CI 1.19–3.2). Including cases of only microbial keratitis (MK) revealed that genotypes in TLR2 SNP rs5743706 TA (p = 0.0001; OR = 8.61; 95 % CI 2.59–28.56)), TLR4 SNP s4986791 TC (p = 0.002; OR = 2.65; 95 % CI 1.39–5.07) were significantly more common for MK, whereas the TLR5 SNP rs2241096 A allele (p = 0.00316, OR = 0.42, 95 % CI 0.2−0.9286) and GA genotype (p = 0.016; OR = 0.45; 95 % CI 0.23−0.86) was significantly less common in MK cases. The TLR2 SNP rs5743706 genotype TA was significantly less common in the sterile keratitis (SK) group (p = 0.004, OR = 0.43, 95 %CI 0.24−0.77). Haplotype analysis of MK compared to controls showed that TLR2 AT was more common in controls (p = 0.003); TLR4 ACAC was more common in cases (p = 0.004); TLR5 TGGCA was more common in controls (p = 0.001). ConclusionThe present study revealed multiple associations between variants across TLR genes, which may have implications for understanding the underlying host factors, risk of developing keratitis and molecular pathogenesis in keratitis.

Profile of infectious and sterile keratitis after accelerated corneal collagen cross-linking for keratoconus.

PURPOSE:The aim of this study was to assess the potential risk factors and causes of infectious and sterile keratitis after accelerated collagen cross-linking.METHODS:Case records of 968 eyes that underwent accelerated corneal collagen cross-linking (ACXL) over the period of 4 years were reviewed retrospectively. ACXL was done using (Avedro KXL® system, Waltham, MA, USA) 9 mW/cm2 for 10 min protocol providing total energy of 5.4 J/cm2.RESULTS:Of 968 eyes, a total of three eyes developed infectious keratitis and seven eyes developed sterile infiltrates. Three of this infectious keratitis had two cases which were resistant to fourth-generation fluoroquinolones. Seven cases of sterile infiltrates had excellent resolution after treatment with topical steroids. Sterile infiltrates were common in corneas with thinnest pachymetry of <400 µm, except in one case of intra stromal corneal ring segments (INTACS) + ACXL.CONCLUSION:Judicious use of steroids in the initial postoperative period is recommended so as to prevent any form of microbial keratitis. Very steep corneas and too thin corneas should be looked with high index of suspicion in view of chances of developing sterile infiltrates.

The effect of water exposure on contact lens storage case contamination

Purpose Microbial contamination of contact lens storage cases is associated with corneal disease ranging from sterile keratitis to sight threatening infections including bacterial and Acanthamoeba keratitis. Given the increasing association between water contact and contact lens-related disease, this study aimed to explore the effect of water contact and storage case contamination in habitual daily wear contact lens users.

Sterile Keratitis

Sterile keratitis shows multiple manifestations. It may occur as an ophthalmological problem but can also be part of a systemic disease, including potentially lethal systemic vasculitis. Diagnosis as well as management of this disease is a challenging task for the ophthalmologist. There are therapeutic principles which apply to all non-infectious cases of keratitis and corneal ulcerations. Specific treatments, however, are determined by the pathogenesis and may differ. Therefore, an accurate diagnosis must guide therapeutic decision making. The correct diagnosis and management of sterile ulcerative keratitis is able to restore the patient's vision in most cases. In potentially lethal systemic disease it may even be able to save the patient's life.

Clinical and microbiological profile of infective keratitis and their antibiotic sensitivity

Clinical and microbiological profile of infective keratitis and their antibiotic sensitivity - IJMR- Print ISSN No: - 2394-546X Online ISSN No:- 2394-5478 Article DOI No:- 10.18231/2394-5478.2019.0003, Indian Journal of Microbiology Research-Indian J Microbiol Res

Sterile keratitis following standard corneal collagen crosslinking: A case series and literature review

Standard corneal collagen crosslinking (S-CXL) is a safe, approved procedure, but it may result in severe pain, early vision loss and possible complications, such as infectious or sterile keratitis, in some cases. We describe four cases of sterile infiltrates after uneventful S-CXL for keratoconus, from diagnosis to medical management with six months of follow-up, reporting their pathophysiological features, and comparing our findings with published reports. We discuss various possibilities for diagnosing sterile infiltration more rapidly. In terms of the pathophysiology of sterile infiltrate formation, we separated our patients into two types, one with sterile infiltrate from an antigen reaction and the other with sterile infiltrate due to excessive scarring. Early local steroid treatment resulted in a good visual outcome in our cases.

Femtosecond-assisted intracorneal ring segment complications in keratoconus: from novelty to expertise.

ObjectivesTo document the difference between complication rate in the early curve of practicing intracorneal stromal rings and after gaining experience.Patients and methodsA retrospective study of 623 eyes of 417 patients with keratoconus who underwent Keraring implantation using femtosecond laser for channel creation.ResultsThe main outcome measures were reported intraoperative and postoperative complications. The overall complication rate was 12.7% (79 eyes) over the 4 years with 34 eyes in the first year (5.5%) and six eyes in the fourth year (0.96%). Over the 4 years of our practice, intraoperative complications were 7.1% and postoperative complications were 5.6%. Yet, there was a significant difference in intraoperative complications between the first and the fourth year where it was 3.5% and 0.48%, respectively. This also applies to the postoperative complication rate, which decreased from 1.9% to 0.5% in the fourth year.ConclusionComplications with femtosecond-assisted intracorneal stromal ring procedure can be reduced by experience, making this procedure a safe and effective means of treating keratoconus. Yet, there are some complications that cannot be avoided such as sterile keratitis.

Sterile keratitis after uneventful corneal collagen cross-linking in a patient with Axenfeld-Rieger syndrome

To report on a keratoconus (KC) patient with Axenfeld-Rieger syndrome (ARS) who developed sterile keratitis after accelerated corneal collagen cross-linking (CXL). An 18-year-old patient with ARS and KC who had previously undergone intrastromal ring segment implantation underwent accelerated CXL (9mW/cm2UVA intensity for 10min). After uneventful surgery, the patient presented with severe photophobia, redness of the eye, and decreased vision 72h following the procedure. Slit-lamp examination showed anterior multiple superficial stromal infiltrates in the central cornea with an overlying epithelium defect. Due to the lack of pain and absence of any pathogen from corneal samples, a diagnosis of sterile keratitis was considered. A combination of topical antibiotic and corticosteroid regimen was administered. Three months after CXL slit-lamp examination showed a mild stromal scar overlying the central cornea, which did not decrease visual acuity. The mechanism by which the sterile keratitis occurs following CXL remains unclear. For our case, the reason of post-CXL sterile keratitis could be considered as an immune response due to the staphylococcal antigens. Furthermore, the possible developmental disturbance of corneal stroma in ARS might have contributed to the development of post-CXL sterile keratitis.

Sterile keratitis post collagen cross-linking (CXL) therapy for treatment of keratoconus

Corneal collagen cross-linking therapy is a relatively new treatment for progressing corneal ectasias such as keratoconus. Here the authors discuss the case of a 22-year-old male who underwent collagen cross-linking for treatment of progressive keratoconus, who then developed a serious post operative complication of a sterile keratitis.

Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of Reported Cases: Management, Visual Outcome, and Treatment Proposed

Aim: To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment proposed. Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search from October 2000 to October 2013 was performed to identify all articles describing infectious keratitis following corneal crosslinking treatment. Nineteen articles were selected. Ten articles reported infectious complications of corneal crosslinking treatment were included. Nine articles were excluded, because seven described sterile keratitis, one article was in German, and one reported general complication without describing the infection complication. Results: A total number of infections reported included 10 eyes. The infectious keratitis was associated with bacteria in five eyes (50%): gram-positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes, fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one eye (10%). Conclusions: Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.

Sterile keratitis after combined riboflavin-UVA corneal collagen cross-linking for keratoconus.

To investigate patient risk factors and to look for potential causes of sterile infiltrates following an unexpected cluster of sterile keratitis after a routine collagen cross-linking (CXL) list. The records of all 148 cases of CXL were reviewed retrospectively. The equipment and solutions used and our clinic's standard operating procedure for CXL were reviewed. An in-vitro experiment to explore the variation in ultraviolet A (UVA) irradiance from fluctuations in the working distance of the UVA lamp was conducted. The four patients who developed sterile infiltrates had steeper maximum corneal curvatures (68.0±7.3 D) and thinner pachymetry (389.9±49.0 μm) than the 144 who did not (57.0±8.2 D, P=0.05; 454.6±45.4 μm, P=0.08). A corneal curvature of >60 Dand a pachymetry of <425 μm were significant risk factors. All four affected cases obtained a complete resolution with topical antibiotics and steroids. The unaided VA and the maximum K improved from their pre-operative levels in three out of four patients. A 2-mm reduction in distance of the VEGA C.B.M. X-Linker from a treated surface increased irradiance to 3.5-3.7 mW/cm(2), which is above the threshold for endothelial toxicity. Patients with thinner and steeper corneas are at an increased risk of developing sterile keratitis. The visual outcomes despite this complication are good.

Sterile keratitis after corneal collagen crosslinking in a child

Corneal collagen crosslinking (CXL) is a non invasive technique used in halting the progression of keratoconus. Complications with this modality are rare. We report a case of an 8-year-old child who developed sterile infiltrates in the immediate postoperative period after uneventful corneal collagen crosslinking for keratoconus. The infiltrates resolved with topical steroid therapy. There was also present coexisting vernal keratoconjunctivitis (VKC) which was controlled with topical 2% cyclosporine A eye drops prior to crosslinking treatment. This case highlights importance of controlling VKC prior to CXL in keratoconus as it adds to the risk of developing post operative sterile keratitis.

Association of Single Nucleotide Polymorphisms of Interleukins-1β, -6, and -12B with Contact Lens Keratitis Susceptibility and Severity

To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Retrospective, case control study. One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003 through 2005. Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1β (-31), IL-6 (-174, -572, -597), and IL-12B (3'+1158) genotypes were analyzed with pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis, controls) and severity. Statistical significance was set at 0.05. The relative risk of developing contact lens-related keratitis and more severe forms of the disease based on allele, genotype, and haplotype associations. Carriers of IL-6 SNPs were more likely to experience moderate and severe events compared with those with nonmutated genotypes (-174 heterozygous: odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.3; homozygous: OR, 6.4; 95% CI, 1.4-28.4; -174/-597: OR, 4.1; 95% CI, 1.6-11.0). More severe keratitis and microbial keratitis were less likely to occur in wearers with the nonmutated IL-6 haplotype (severity OR, 0.4 [95% CI, 0.2-0.7]; microbial OR, 0.6 [95% CI, 0.4-0.9]). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR, 9.7; 95% CI, 1.2-76.9) compared with controls. The IL-6 SNPs are known to reduce protein expression of this cytokine and thus ocular immune defense, and carriers of these SNPs were more likely to experience more severe and microbial keratitis, suggesting that IL-6 decreases the severity and susceptibility of contact lens-related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition.

Keratopathy After Cross-linking for Keratoconus

To report 2 cases of keratopathy after uneventful cross-linking procedures for grade 3 keratoconus. Two patients (21 and 11 years old) with grade 3 keratoconus underwent uneventful cross-linking in 1 eye. In both patients, multiple peripheral stromal precipitates, which extended centripetally, were observed 48 hours after the procedure. Sample cultures were negative for bacteria, fungi, and parasites. Cornea infiltrates slowly resolved after combined topical antibiotic/antifungal/povidone/steroids treatment. Final best spectacle-corrected visual acuity was 20/25 for patient 1, after uneventful bilateral toric intraocular contact lens (ICL) (Staar Surgical) implantation, but faint and paracentral scarring persisted. Final best-corrected visual acuity was 20/25 for patient 2 with gas-permeable contact lens wear, despite stromal scarring. Cross-linking associated with sterile keratitis is an unusual entity of unknown etiology, which can lead to stromal scarring.