The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1.

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of First Healthcare Provider on Acanthamoeba Keratitis Course: How to Overcome Poor Prognosis in Acanthamoeba Keratitis Treatment? A Single Tertiary Center, Observational Study.

Background: To assess the difference in course and final visual outcome of Acanthamoeba keratitis (AK) patients based on the first healthcare provider (HCP) seen. Methods: Retrospective observational cohort study of AK patients admitted to the Manchester Royal Eye Hospital between 2003 and 2017. HCPs were grouped (Group 1: Optometrists, Opticians; Group 2: General Practitioners (GPs); Group 3: Ophthalmologists) and the data analyzed on demographics, risk factors, clinical history, clinical features, and Acanthamoeba subspecies. Results: Forty-one patients with unilateral culture-proven AK were included. Median time to consultation with first HCP was 7 days (IQR 4-14 days), while mean time to the correct diagnosis of AK was 15 days (IQR 7-29 days). Patients saw an optician, optometrist or ophthalmologists significantly earlier than GPs (median 4 days, vs 15 or 5 days, respectively, p = 0.04). Bacterial keratitis was the most common initial clinical diagnosis (43%). The shortest time to making the AK diagnosis (median 11 days) and the highest rate of initiating AK treatment started at the first visit (38%) were both in the ophthalmologists' group. No significant differences were observed in initial and final visual acuity between HCP groups (p = 0.36). Conclusion: AK patients often seek ocular help earlier from optometrists and opticians than medical doctors. Final clinical outcomes did not significantly differ based on the first HCP seen, but ophthalmologists were more likely to make the diagnosis of AK and initiate anti-amoebal therapy faster than other HCPs. Greater education and collaboration between ophthalmologists and other HCPs to increase awareness of AK are needed.

Impact of the COVID-19 Pandemic on the Incidence and Characteristics of Culture-Positive Microbial Keratitis at a Tertiary Eye Hospital in the UK.

Purpose: The COVID-19 pandemic has led to drastic changes to the daily lives of those living in the United Kingdom. We hypothesized that the effect of the imposed lockdown on both behaviour and social interaction has the potential to influence the characteristics of microbial keratitis presenting locally to Manchester Royal Eye Hospital - a major tertiary eye centre in the UK. Methods: We conducted a retrospective case-note review of all positive corneal scrape cultures identified by our local microbiology laboratory during the year since the announcement of lockdown measures in the UK (23 March 2020 to 23 March 2021). Culture results were compared with previously collated, published "baseline" data from prior to the onset of the COVID-19 pandemic (2004-2019). Statistical analysis was undertaken, predominantly looking at the incidence of microbial keratitis and the variety of cultured pathogens. Results: A total of 6243 corneal scrape results were reviewed. Comparison of data between the COVID-19 pandemic and subsequent lockdown did not show a significant change in the incidence of culture-positive microbial keratitis: mean annual positive samples during 2004-2019 were 128 (35%) vs 91 (29%) during lockdown (P=0.096). No statistically significant shifts in the incidence of organism subtypes - fungi, acanthamoeba, Gram-positive bacteria, or Gram negative bacteria - were identified (P=0.196, 1, 0.366, and 0.087, respectively). Conclusion: Contrary to our hypothesis, our results suggest that the COVID-19 pandemic did not alter the incidence or characteristics of microbial keratitis presenting to Manchester Royal Eye Hospital in the year following the implementation of lockdown measures in the UK.

Corneal Decompensation in Uveitis Patients: Incidence, Etiology, and Outcome.

Purpose: To identify the prevalence, etiology, management and visual outcomes of treatment in uveitis-related corneal decompensation.Patients and methods: This is a retrospective study of patients with corneal decompensation identified from a large cohort with uveitis in a tertiary referral clinic setting.Results: Between March 1991 and May 2018, 4132 new patients with uveitis were seen in Manchester Uveitis Clinic. Of these, 25 patients (0.6%) were identified with corneal decompensation of which 9 (0.2%) were affected bilaterally (total 34 eyes). The mean interval between uveitis diagnosis and decompensation was 23 months (range 0-117 m). Ten patients (41%) had associated glaucoma. Seventeen eyes (50%) had undergone intraocular surgery prior to decompensation. For eyes with no history of raised intraocular pressure or intraocular surgery, keratouveitis (presumed autoimmune or tuberculous) was the most common cause of corneal decompensation. Fourteen eyes (41%) required corneal graft and of these, five required repeat grafting.Conclusions: Corneal decompensation in eyes with uveitis is a rare but significant complication. Direct endothelial inflammation may alone cause decompensation, but in most eyes with uveitis, prior raised intraocular pressure or intraocular surgery are required to precipitate the cornea into decompensation. Outcomes of corneal transplantation in this group may be disappointing.

Microbial Keratitis in Corneal Transplants: A 12-Year Analysis.

PURPOSE: To investigate the frequencies, trends, and in vitro drug susceptibilities of the causative pathogens in corneal transplant microbial infections in Manchester Royal Eye Hospital. METHODS: Corneal scrape results recorded by the microbiology service between 2004 and 2015 were extracted from an established database. This microbiological data was matched with a separate database of all corneal transplant procedures performed in our centre over this time period. Patient records were examined to collect specific patient data and to confirm the diagnosis of microbial keratitis. RESULTS: A total of 1508 grafts had been performed at our centre in this period. 72 episodes of graft microbial keratitis were identified from 66 eyes that had undergone keratoplasty procedures. Mean age was 56, and 51% of subjects were male. Ninety-three percent of microbial keratitis episodes occurred in penetrating keratoplasty procedures and 6% in deep anterior lamellar keratoplasty procedures. No endothelial grafts presented with infections throughout this time period. Of the 79 organisms identified, 73% were gram positive, 23% gram negative and 4% fungi. With regard to gram-positive organisms, vancomycin and gentamicin showed 100% and 91% susceptibility, respectively. Ofloxacin had a resistance rate of 13.7%. In terms of gram-negative organisms, gentamicin and chloramphenicol showed 100% sensitivity, with cefuroxime showing 69%. Resistance rates were less than 15% in all tested gram-negative antimicrobials. CONCLUSION: This paper describes the largest collection of corneal transplant infections identified within the UK. This finding may aid clinicians in predicting possible causative organisms for microbial keratitis and aid antibiotic choice.

Subconjunctival Ab Externo Gel Stent Implantation for Refractory Glaucoma After High-Risk Penetrating Keratoplasty.

This case study reports the successful deployment of the XEN45 gel stent (AbbVie Inc, Chicago, IL) through an ab externo approach in a 73-year-old woman with refractory glaucoma following high-risk penetrating keratoplasty (PK) 10 years prior. The PK was for corneal perforation secondary to peripheral ulcerative keratitis, which required systemic immunosuppression comprising intravenous cyclophosphamide, azathioprine, and corticosteroids to stabilise the disease and prevent corneal graft rejection. The patient's intraocular pressure was reduced from 40 mmHg preoperatively to 12 mmHg six months after surgery, off medication. The patient's visual acuity and visual fields remained stable. The XEN45 gel stent utilising the ab externo approach can be considered as a potential tool to lower intraocular pressure in patients with glaucoma after corneal keratoplasty.

Next-Generation Sequencing of the Ocular Surface Microbiome: In Health, Contact Lens Wear, Diabetes, Trachoma, and Dry Eye.

OBJECTIVES: To assess publications examining the occurrence, composition, and clinical significance of a microbiome at the ocular surface. METHODS: MEDLINE, EMBASE, and Google Scholar were searched. Reference lists of included articles were also searched for relevant citations. All publications up to June 1, 2019, were analyzed. RESULTS: Eleven articles and 1 abstract were included, analyzing 661 patients. Articles generally report bacteria to the genus level. The presence of DNA associated with diverse bacterial species was reported including pathogenic species, such as Pseudomonas and Neisseria. Bacterial DNA that makes up the microbiome, such as Acinetobacter, Actinomyces, Aquabacterium, Bradyrhizobium, Corynebacterium, Sphingomonas, Staphylococcus, and Streptococcus, in other parts of the body was found. The putative ocular microbiome is consistent between right and left eyes and is affected by contact lens use (higher Pseudomonas levels) and blepharitis (higher Staphylococcus levels). CONCLUSIONS: There is a significant likelihood that there is at least a transitory ocular surface microbiome, with Acinetobacter, Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus detected in at least 7 of 11 studies. However, further investigation attempting to control for environmental and methodological contaminants (Aquabacterium and Bradyrhizobium are commonly identified as contaminants in DNA extraction kits) is required. Bacteria, such as Propionibacterium, Staphylococcus, and Streptococcus, capable of causing sight-threatening infections may reside on a healthy ocular surface. With greater understanding, we can establish whether elements of the ocular surface microbiome are harmful or protective (despite their small quantities); furthermore, new therapeutic agents can be identified to treat and prevent ocular surface infection and inflammation.

Management of penetrating injury with retained intraocular lead foreign body from a writing instrument: surgical video with implications for paediatric public health and safety.

Penetrating ocular injuries from writing instruments that are thrown, especially by children, in the community can result in significant ocular morbidity. Often these cases present to the accident and emergency department. Accurate and prompt assessment is key in saving sight. We present a case of one such injury and how it was surgically managed.

Corneal Imaging and Densitometry Measurements in Juvenile and Adult Keratoconus Patients to Evaluate Disease Progression and Treatment Effects After Corneal Cross-Linking.

PURPOSE: In this study densitometry software for the Oculus Pentacam was used to investigate the treatment outcomes of corneal cross linking (CXL) in adult and juvenile keratoconus (KCN) patients. Densitometry measurements were taken before and after treatment and followed up for one year. METHODS: A comparative study was carried out at Manchester Royal Eye Hospital. Corneal densitometry measurements collected before and after CXL treatment for 32 eyes from KC patients, aged between 12 and 39, were divided to 2 groups 13-18 years (juvenile group) and 19-39 years (adult group) and analysed and compared to pre and post treatment at 3, 6 and 12 months for each group and between both groups. RESULTS: Analysis of densitometry measurements found higher corneal densitometry after CXL which peaks at three months post treatment in both groups. There was significant diversity in corneal densitometry measurements in the stromal zone 0-2 and 2-6 mm for all layers except the posterior layer for both groups (P<0.05). Significantly increased densitometry value was found higher in the juvenile group at six months in the central (P=0.006) and posterior (P=0.004) layers for zone 0-2 mm. The same layers differed significantly also in the 2-6 mm zone in all layers (P=0.01). One year post treatment the same significant increased densitometry level was seen in the juvenile group in the 0-2 mm zone of the central (P=0.007) and posterior layers (P=0.01), as was the 2-6 mm zone (P=0.04). However, no significant difference was found between pre and post treatment for best corrected visual acuity (BCVA), central corneal thickness (CCT) and thinnest area between both groups. A significant difference was found between pre and post treatment for best corrected visual acuity (BCVA), in the adult group at 6 and 12 months post-treatment from pre-treatment (P=0.02, P=0.16) respectively. CONCLUSION: Corneal clarity post CXL treatment in the juvenile group differed significantly from the adult group. Both groups showed increased haze at 3 months post treatment but the adults showed improvement over the next 9 months. In contrast, the juvenile group showed higher densitometry readings at both 6 and 12 months post treatment in comparison to adult group. The reasons for this remain unclear.

Corneal imaging and densitometry measurements in keratoconus patients to monitor disease progression and treatment outcomes after contact lens or Intacs treatment.

AIM: The aim of this study was to compare the pre- and posttreatment corneal densitometry and corneal thickness value of keratoconus (KCN) patients managed via contact lenses (CLs) or by both intrastromal corneal rings and contact lenses. PATIENTS AND METHODS: This prospective study was performed at the Manchester Royal Eye Hospital, UK. Patients were recruited before treatment and followed up for 12 months. Data of corneal densitometry and corneal thickness were collected using the Oculus Pentacam at the pretreatment visit and posttreatment visit at 12 months. RESULTS: Corneal clarity significantly differs between both groups at pre treatment at zone 0-2 mm for the anterior layer (P=0.002). The same diversity is present at zone 2-6 mm for the anterior layer (P=0.003) and posterior layer (P=0.008). The corneal clarity diversity found was not statistically significant at 12 months post treatment (P>0.05). Corneal thickness was found to be statistically significantly different between pre treatment and post treatment for the CL group for central corneal thickness (CCT) and thinnest area (P=0.01 and P=0.02), respectively. DISCUSSION: This study shows that KCN management with Intacs was found to be effective in maintaining corneal clarity for a longer time than that with CL alone. On the other hand, corneal clarity reduces with disease progression in cases managed with CLs only. Analysis of Oculus Pentacam images provides an objective evaluation to monitor the corneal status after these different pathways of management.

Association Between Season, Temperature and Causative Organism in Microbial Keratitis in the UK.

PURPOSE: Microbial keratitis (MK) is a major cause of corneal blindness worldwide. Variations in season and temperature can affect MK incidence due to specific causative organisms; however, few studies have examined these factors in the UK. METHODS: Retrospective review of all corneal scrapes from patients with MK presenting to Manchester Royal Eye Hospital, UK, between January 2004 and December 2015. Manchester's monthly temperature data were obtained from Met Office UK. Analysis was performed using logistic regression. RESULTS: From 4229 corneal scrapes, 1539 organisms grew (90.6% bacteria, 7.1% fungi, and 2.3% Acanthamoebae sp.). Gram-positive bacteria grew with increasing temperature [odds ratio (OR) 1.62, 95% CI: 1.11-2.39, P = 0.014], and fungi grew with decreasing temperature (OR 0.29, 95% CI: 0.16-0.51, P < 0.001). Moraxella sp. grew with decreasing temperature (OR 0.91, 95% CI: 0.86-0.96, P = 0.001). Compared with winter, overall culture positivity was significantly less likely in summer (OR 0.57, 95% CI: 0.38-0.87, P = 0.008) and spring (OR 0.65, 95% CI: 0.43-0.99, P = 0.045). Gram-negative bacteria were more likely in summer (OR 1.48, 95% CI: 1.06-2.09, P = 0.022) and autumn (OR 1.75, 95% CI: 1.24-2.47, P = 0.001). Candida sp. were less likely in summer (OR 0.25, 95% CI: 0.07-0.82, P = 0.027) and autumn (OR 0.18, 95% CI: 0.05-0.62, P = 0.009), and Acanthamoeba sp. were less likely in summer (OR 0.39, 95% CI: 0.15-0.92, P = 0.037) and spring (OR 0.26, 95% CI: 0.08-0.69, P = 0.011). CONCLUSIONS: Herein we report variation in the incidence of MK-causing organisms by season and temperature; this finding may aid clinicians in predicting possible causative organisms for MK at differing times of the year.

Clinical Characteristics and Outcomes of Moraxella Keratitis.

PURPOSE: Changing trends of infective keratitis have been identified worldwide. The aim of this study was to define the clinical associations, characteristics, and outcomes of patients with culture-proven Moraxella keratitis from a large tertiary corneal unit in the United Kingdom. METHODS: Patients with confirmed Moraxella isolates presenting between January 2004 and November 2016 were analyzed. Patient-related factors were examined, including patient demographics, date of presentation, clinical presentation, predisposing factors, best-corrected visual acuity (BCVA), treatment plans, and clinical outcomes. RESULTS: Eighty-six patients were identified, of whom 61 (70.9%) had at least one recognized predisposing factor. The median BCVA at presentation was 2.60 logarithm of the minimum angle of resolution (logMAR), which improved to median = 0.60 logMAR at final visit (P < 0.001). Visual improvement of more than 2 Snellen lines was achieved in 60.7% of eyes. A significant relationship (P = 0.003) between final vision and the presence of hypopyon was found, where for a fixed BCVA at presentation those with a hypopyon achieved a better final visual acuity of 0.69 logMAR. CONCLUSIONS: Our study showed that although most patients presented with at least one predisposing factor, some of the more traditionally perceived risk factors may need to be reconsidered. We have shown that with aggressive treatment, favorable visual outcomes can be achieved in most patients. Interestingly, the presence of hypopyon at presentation was linked to a better visual outcome, likely because such patients had more to gain in visual potential.

Corneal clarity measurements in patients with keratoconus undergoing either penetrating or deep anterior lamellar keratoplasty.

PURPOSE: To compare the corneal clarity measurement between penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) in patients with keratoconus, using densitometry software for the Oculus Pentacam. METHODS: A retrospective comparative study was carried out at Manchester Royal Eye Hospital. Data were collected 12-18 months after corneal transplantation for keratoconus, including postoperative corneal densitometry, best corrected visual acuity (BCVA), central corneal thickness (CCT), and other relevant clinical details. RESULTS: Analysis of 37 keratoconus eyes from 36 patients found there was a significantly higher corneal densitometry measurement after DALK than PK. This was predominantly in the posterior layer of the concentric zone 0-2 mm of the cornea (P=0.0004). A significant correlation was found between postoperative BCVA and corneal densitometry in DALK groups at full thickness (P=0.03). This correlation was seen in the central 0-2 mm (P=0.03) and posterior 0-2 mm (P=0.04) zones. In addition, within the DALK group, a correlation was found between central corneal thickness and densitometry at full thickness 2-6 mm (P=0.007), central 0-2 (P=0.04), central 2-6 mm (P=0.01), and at posterior 2-6 mm (P=0.01) zones. CONCLUSION: This study showed that corneal densitometry measurement differs depending on the type of corneal transplantation used to treat keratoconus patients. Densitometry may have an important role to play in the final BCVA achieved by patients undergoing corneal transplantation for keratoconus. Analysis of Oculus Pentacam images provides an objective evaluation to monitor the cornea status after the surgery.

Evaluation of corneal symmetry after UV corneal crosslinking for keratoconus.

PURPOSE: The purpose of this study was to assess UV corneal crosslinking (CXL) treatment outcomes for keratoconus by evaluating the corneal regularity in patients through follow-up using the Oculus Pentacam. PATIENTS AND METHODS: A total of 18 eyes from CXL patients with keratoconus were studied before and after CXL treatment, and six eyes from six patients who were not treated with CXL served as controls. Treated patients had Pentacam images taken before CXL treatment and regularly 3 months post treatment up to the 12th month. Controls were imaged during their first appointment and after 12 months. Symmetry and asphericity were evaluated and correlated with both best-corrected visual acuity (BCVA) and maximum K-readings. RESULTS: In the CXL-treated group, there was a significant improvement in the index of symmetrical variation (ISV) and keratoconus index (KI) at 3 months and in the index of height asymmetry (IHA) and minimum radius of curvature (Rmin) at 9 months post treatment. On the contrary, the untreated group's indices showed some significant worsening in ISV, KI, central keratoconus index (CKI), and Rmin. A novel finding in our study was a slight positive shift of anterior asphericity in the 6 mm, 7 mm, and 8 mm 3 months after treatment, which had a correlation with BCVA (R2=0.390, p=0.053) and a strong correlation with maximum K-reading (R2=0.690, p=0.005). However, the untreated group had no significant changes after 1 year. CONCLUSION: The corneal asymmetrical shape is associated with the spherical aberration alteration influenced by temporal evolution of surface ablation and increased corneal haze. However, insignificant changes in symmetry attest the stabilization effect on cornea postoperatively as compared with controls.

Corneal clarity measurements in healthy volunteers across different age groups: Observational study.

The aim of this study was to standardize and investigate the changes in corneal clarity with age. Densitometry software for the Oculus Pentacam was used to examine corneal clarity at different age groups.A total of 192 eyes from 97 healthy participants were included in this cohort comparative nonrandomized, cross-sectional study. An Oculus Pentcam was used to image the cornea of healthy participants grouped by age (between 10 and 70 years old). Data from the densitometry output have been used to determine clarity in concentric zones and different depths of the cornea.Corneal densitometry (CD) across all ages showed significant differences between groups when divided into the following layers: anterior, central, and posterior or divided into 0 to 2, 2 to 6, and 6 to 10 mm concentric zones (P < .05). The most striking decrease in clarity occurred with age in all 3 layers of the periphery (6-10 mm) (P < .05). In addition, we showed that the 10 to 19-year age group had lower clarity than the 20 to 30-age group (P < .05), and after 30 years, the cornea shows a steady progression of increased or decreased clarity.The values for CD, as well as for separate subdivisions based on layer and surface area, might provide a standard for use in further studies and clinical practice. This study established that relation between CD and age is differed when the cornea is divided into layers and zones. This study suggests that there are other factors that may play an essential role in corneal clarity as well as age.

Evaluation of Corneal Cross-Linking for Treatment of Fungal Keratitis: Using Confocal Laser Scanning Microscopy on an Ex Vivo Human Corneal Model.

Purpose: Some previous reports have established the use of photoactivated chromophore-induced corneal cross-linking (PACK-CXL) in treating fungal keratitis. The results of these case reports have often been conflicting. To systematically study the effect of PACK-CXL in the management of Fusarium keratitis, we have developed an ex vivo model of human corneal infection using eye-banked human corneas. Methods: Sixteen healthy ex vivo human corneas were divided into four study groups: (1) untreated control, (2) cross-linked, (3) infected with fungal spores, and (4) infected with fungal spores and then cross-linked. All infected corneas were inoculated with Fusarium oxysporum spores. The PACK-CXL procedure was performed 24 hours post inoculation for group 4. For PACK-CXL treatment, the corneas were debrided of epithelium; then 1% (wt/vol) isotonic riboflavin was applied dropwise at 5-minute intervals for 30 minutes and during the course of UV-A cross-linking for another 30 minutes. The corneas were imaged using a confocal microscope at 48 hours post inoculation, and the Fusarium hyphal volume and spore concentration were calculated. Results: The infected and then cross-linked group had a significantly lower volume of Fusarium hyphae, compared to the infected (P = 0.001) group. In the infected and then cross-linked group there was significant inhibition of Fusarium sporulation compared with the infected (P = 0.007) group. Conclusions: A model of human corneal infection was successfully developed for investigation of the effects of PACK-CXL on fungal keratitis. A treatment regimen of combined UV-A/riboflavin-induced corneal cross-linking appears to be a valuable approach to inhibit the growth and sporulation of Fusarium and suppress the progression of fungal keratitis.

Tomographic indices as possible risk factors for progression in pediatric keratoconus.

PURPOSE: To determine whether corneal tomography can help predict the risk of progression of keratoconus in children. METHODS: The medical records of pediatric patients with keratoconus presenting to a large tertiary institution in the UK from 2009 to 2014 were reviewed retrospectively. Patients underwent serial clinical examination and corneal tomography. The minimum follow-up period was 5 months. Patients with a history of eye surgery including corneal crosslinking were excluded. The following tomographic parameters were analyzed: thinnest corneal thickness (TCT), average central corneal keratometry (Km), and maximum central posterior elevation (MCPE). The rate of progressive corneal thinning, in µm/month, was calculated as the difference between TCT on presentation and at the most recent visit divided by the time in months. RESULTS: A total of 36 eyes of 19 patients (10-16 years of age) were included. Mean follow-up was 19 months (range, 5-30 months). Six eyes (17%) developed corneal scarring and 1 eye (3%) developed acute hydrops. Of the 29 eyes that did not develop corneal scarring or hydrops, 24 (83%) demonstrated progressive corneal thinning over the period of the study. Eyes with TCT of <450 µm, Km above 50 D, and MCPE above 50 µm at presentation demonstrated the highest rates of progressive corneal thinning over the study period. CONCLUSIONS: In pediatric keratoconus, lower TCT, higher Km, and higher MCPE on corneal tomography seem to be risk factors for faster rates of progressive corneal thinning.

Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact Lens Delivery System.

PURPOSE: The corneal epithelium is sloughed off surface of the eye by the action of blinking and is continually replaced by division and maturation of the limbal stem cells (LSCs). In the case of injury or disease, LSCs can be lost or damaged to a point at which the corneal epithelial layer is no longer maintained. leading to LSC deficiencies (LSCDs). When this occurs, the opaque conjunctiva overgrows the anterior surface of the eye, leading to vision impairment or loss. Dental pulp stem cells (DPSCs) are promising candidates as autologous LSC substitutes. In this study, contact lenses (CLs) are used as a novel medical device to deliver DPSCs onto corneal surface to enhance corneal epithelium regeneration. METHODS: Dental pulp stem cells labeled with green fluorescent Qtracker 525 were seeded onto the pretreated CLs, allowed to adhere, then delivered to debrided human corneas. Expression of KRT3, 12, 13, and 19 was investigated by immunostaining, then standard and confocal microscopy. RESULTS: Dental pulp stem cells were successfully isolated, labeled, and delivered to the corneal surface using CLs. Following removal of CLs, confocal microscopy showed that the DPSCs had migrated onto the cornea. Coexpression of KRT12 and green fluorescent Qtracker 525 confirmed that the DPSCs had transdifferentiated into corneal epithelial progenitors. Delimitation of KRT 19 and green fluorescence provides evidence that Qtracker 525-labeled DPSCs establish a barrier to the invasion of the cornea by conjunctiva. CONCLUSIONS: In this study we show that DPSCs, delivered using CLs, can be used to enhance repair and regeneration of the human corneal epithelium.