Each year, eye care practitioners are provided with an opportunity to gain insight on the latest groundbreaking research in vision science. And, this year’s Association for Research in Vision and Ophthalmology (ARVO) annual meeting, held May 6-10 in Ft. Lauderdale, Fla., delivered. Research presented at this annual event helps practitioners formulate best practices through evidence-based science and stimulates researchers to ask, and attempt to answer, additional questions pertinent to clinical practice.
This year’s abstract review topic was microbial keratitis—an important conversation due to the devastating consequences the disease leaves in its wake. The abstracts presented at ARVO were teeming with helpful tools designed to help the practitioner develop new strategies, direct treatment plans and ultimately improve patient outcomes.
Pseudomonas aeruginosa Keratitis: Pathogen Genotype Impacts Clinical Presentation and Outcomes
Researchers from UC San Francisco, UC Berkeley School of Optometry and the Aravind Eye Hospital in Madurai, India assessed how cytotoxicity and invasiveness, two P. aeruginosa virulence factors, affect clinical outcomes and corneal baseline characteristics. Ulcers caused by P. aeruginosa with the invasive genotype presented with better visual acuity, but were associated with less improvement at three months when compared to cytotoxic ulcers. Steroids were associated with better outcomes for invasive P. aeruginosa corneal ulcers but with worse outcomes for cytotoxic ulcers. A tailored treatment approach by genotypic subtype using PCR testing may be advisable for P. aeruginosa keratitis.
Virulence Factors in Pseudomonas aeruginosa Keratitis
Researchers in Liverpool, United Kingdom, identified virulence factors in cases of P. aeruginosa keratitis to be used in personalizing treatments and prognosis. Clinical outcome data showed that clone A, serotype 011 and the presence of exoS were associated with prolonged healing time, larger corneal ulcers and gentamicin resistance. Identification of clonal type and virulence factor exoS is of prognostic significance. When these factors are present in patients with P. aeruginosa keratitis, it may help future therapies and target treatment.
The Role of Dendritic Cells in Flagellin-Induced Protection Against Pseudomonas aeruginosa Keratitis
Researchers at Wayne State University and the Kresge Eye Institute in Michigan studied underlying mechanisms for flagellin-induced dendritic cell (DC) recruitment and/ or activation and defined their role in corneal innate defense. Dendritic cells are recruited and/or activated in the cornea’s response to flagellin. Deletion of DCs increased corneal susceptibility to P. aeruginosa and abolished flagellin-induced protection in B6 mice. Dendritic cells play a critical role in corneal innate immunity and defining their role opens a new area of investigation.
Genotypic Characterization of Staphylococcus aureus Isolated from Eyes with Keratitis
Researchers at the Ehime University Graduate School of Medicine in Toonishi, Japan investigated the genotypic characterization of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates from eyes with keratitis and healthy conjunctival sacs. MRSA isolates from eyes with keratitis have genotypic characteristics similar to those of commensal MRSA strains, but certain sequences occur more often in MSSA isolates from eyes with keratitis than in commensal MSSA strains.
The results suggest that MSSA lineages with specific genotypic characteristics are more likely to cause keratitis. S. aureus remains a common ocular pathogen with emerging resistance in practice. Additional research looking at the virulence of particular lineages should aid in the management of these common corneal infections.
Molecular Characterization of Virulence Genes Associated with MRSA Keratitis Isolates
Researchers at the Bascom Palmer Eye Institute in Miami identified and characterized the molecular spectrum and frequency of virulence genes associated with MRSA isolates recovered from keratitis. Findings revealed that MRSA isolates recovered from keratitis are predominantly healthcare-related (SCCmec II), PVL negative and harbor the quorum-sensing genotype for vancomycin heteroresistance (agrII). This combination of virulence genes may impact efficacy and selection of antibiotic prophylaxis, and therapeutic management of patients with MRSA keratitis.
Acanthamoeba-Associated Microbial Communities
Researchers at the Bascom Palmer Eye Institute, University of Miami School of Medicine and the University of Washington School of Medicine, used a combination of metagenomics and next-generation sequencing techniques to document the presence, complexity and diversity of Acanthamoeba-associated microbial communities in isolates recovered from patients with amoebic keratitis. Culture-independent molecular methods reveal complex and diverse Acanthamoeba-associated microbial communities in clinical isolates. Community complexity and diversity may impact clinical severity, course and time to cure. Acanthamoeba may harbor unique microbiomes that might contribute to the severity of the disease.
Bilateral Herpetic Keratoconjunctivitis in Cancer Patients
This study, conducted at the University of Texas in Houston, is the first in literature to retrospectively review and describe bilateral HSV and HZV keratoconjunctivitis in 90 cancer patients. It was most frequently observed in patients on systemic steroids and an immune-compromised patient population despite prophylaxis for herpetic disease. Bilateral presentations signal concern for atopy (cited in past research) or an immune-compromised state possibly in occult cancer patients. Future studies are necessary to elucidate predisposing factors for bilateral disease in this population.
Boston Type 1 Keratoprosthesis: Microbial Colonization and Antibacterial Resistance
Investigators at the Hospital of the University of Montreal characterized the ocular flora of patients who had the boston keratoprosthesis (KPro) implantation. The KPro implant imparts lifelong risk for keratitis and endophthalmitis. Patients with the KPro were more likely than controls to colonize fluoroquinolone (FQ)-resistant Staphylococci (coagulase negative). The researchers blame the chronic use of FQ for prophylaxis as the main reason for antibiotic resistance and recommend modifications in prophylaxis in order to prevent emergence of resistant pathogens. One option may be to rotate antibiotics periodically.
Risk Factors for Contact Lens Related Microbial Keratitis: A Prospective Multicenter Case Control Study
Scientists at the Strasbourg University Hospital in France conducted a study to identify risk factors and the social burden of contact lens related microbial keratitis. They cite concern with the increasing availability of contact lenses through the Internet or local market highlighting the need for professional supervision and the lack of information about the basics of hygiene and handling. Of interest, daily disposable lenses and two-week replacement options had a slightly higher relative risk for infection when compared to monthly replacement lenses (maybe due to the lack of basic rules of hygiene, such as lack of hand washing).
The Roles of Epigenetic Factors in the Pathogenesis of Keratitis
Researchers at the Henan Eye Institute in China studied the role of histone deacetylation (HDAC) in the pathogenesis of fungal keratitis. They found the aberrant expression of HDAC in fungal infected corneas. The expression of HDACs and the loss of balance between histone acetylation and deacetylation are the major features of fungal keratitis. Inhibitors of HDAC, like Trichostatin, may play a vital role in the therapeutic management of fungal keratitis.
Treatment of Severe Bacterial Keratitis with Corneal Collagen Crosslinking
Investigators at the Louisiana State University Department of Ophthalmology in New Orleans looked at characterizing the antibiotic effect and induced histological alterations of corneal crosslinking (CXL) in bacterial keratitis. Thirty minutes after CXL, the experimental cornea was significantly less edematous than the antibiotic treated cornea with severe keratitis. Histological evaluation of the stroma showed a tightly-packed and coherent lamellae.
Colony counts showed statistically significant differences between the CXL eyes and controls at 30 minutes. CXL appears to be a useful adjunct to treat corneal infection and to maintain structural integrity of the cornea in severe bacterial keratitis.
Confocal Microscopy: Interpretation of the Clinical Images in Atypical Keratitis
Researchers at the Aarhus University Hospital Department of Ophthalmology in Denmark evaluated the utility of in vivo confocal microscopy (IVCM) in patients with atypical keratitis. They cited an increased frequency of identifying fungal keratitis by localizing highly reflective branching structures, but a decreased ability to recognize Acanthamoeba keratitis (AK) infections. In AK, cysts often lack a visible ring making the organism difficult to recognize from inflammatory cells in the cornea. This finding indicates a higher sensitivity and sensitivity in identifying fungal infections by IVCM than AK.
The Association Between History and Culture Isolates from Bacterial Keratitis Cases in Shanghai
Scientists at the Eye and Ear Hospital of Fudan University in Shanghai studied the microbiologic characteristics of bacterial keratitis cases at their location. They explored the association between history and culture isolates from their patients affected. Low education levels, ocular surface disease, trauma, cigarette smoking and presence of diabetes were linked to increased odds of gram-positive bacterial keratitis. Contact lens wear was the main risk for gram-negative bacterial infections. They suggest that consideration of risk factors may be useful for choosing empiric antibiotic treatment before pathologic bacteria are identified.
Opinions on Bandage Contact Lens Practice in the UK
Researchers at the Royal Victoria Infirmary, United Kingdom, studied the prescribing practices of bandage contact lenses (BCL) among members of the Bowman Club (UK Cornea Society). They were surveyed for opinions regarding indications and prescribing patterns, concomitant medication for prophylaxis and complications related to BCL use. The most common lens use was for pain relief, followed by promotion of healing epithelial defects, for wound apposition and mechanical protection of the ocular surface. A high incidence of secondary corneal ulcers was reported and topical antibiotic usage was only found to be used in 42.3% of the consultant’s surveyed. A final recommendation includes sterile lens insertion using forceps and the use of topical antibiotics for prophylaxis.
Contact Lens-Associated Microbial Keratitis Trends in South India from 2001-2011 from a Comprehensive Eye Care Centre
Investigators at the Brien Holden Vision Institute in Sydney, Australia conducted a retrospective study to review trends of contact lens-associated microbial keratitis (CL-MK) over a decade in an eye health facility in India. Patients were identified with history of contact lens wear and corneal ulcer between September 2001 and November 2011 using laboratory database and medical screening. Over the decade, the rate of CL-MK increased gradually. The predominant microbe isolated was Pseudomonas. Wearer compliance played a significant role and medical therapy provided a good treatment outcome in most cases. There was a gradual increase over the decade in the rate of CL-MK.
Incidence of MRSA/MRSE and Co-Existing Ophthalmic Drug Resistance in Refractive Surgery Seeking Patients
Scientists at the U.S. Army Refractive Surgery Research Program in Virginia conducted a study to report the incidence of MRSA colonization in refractive surgery seeking patients, and to evaluate co-existing resistance to normally prescribed ophthalmic medications. Positive cultures for MRSA/MRSE were found in 16.6% of patients in a high-risk group who presented for refractive surgery evaluations. It should be noted that ocular cultures won’t identify MRSA/MRSE carriers. Coexisting ophthalmic drug resistance to medications used in refractive surgery (including latergeneration FQ) is common.
Infectious Keratitis Progressing to Endophthalmitis: A 15-year-study of Risk Factors, Microbiology and Clinical Outcomes
At the Bascom Palmer Eye Institute, investigators studied the incidence, microbiology, risk factors and clinical outcomes of a consecutive series of patients with infectious keratitis progressing to endophthalmitits. Fifty-two of the 9,934 corneal cultures of patients with infectious keratitis progressed to endophthalmitis. Therefore, progression of infectious keratitis to endophthalmitis is uncommon. This study suggests that patients using topical corticosteroids, those with a fungal keratitis and those developing infectious keratitis adjacent to a previous surgical wound are patients at higher risk for progression to endophthalmitis. Those patients with sequential keratitis and endophalmitits have generally poor vision outcomes.
Long-Term Visual Outcomes, Graft Survival and Complications of Deep Anterior Lamellar Keratoplasty in Patients with Herpes Simplex Related Corneal Scarring
This retrospective non-comparative case series study from the United Kingdom investigated long-term visual outcomes, complications and graft survival of patients undergoing deep anterior lamellar keratoplasty (DALK) to treat corneal scarring secondary to herpes simplex virus keratitis. Patients undergoing DALK for HSV corneal scarring have a higher rate of complications following surgery. Graft failure is uncommon with timely and aggressive therapy. There are a large percentage of secondary operations following DALK in this cohort and adequate informed consent is important when counseling these patients.
Hope you enjoy this year’s review. If you are interested in reading through additional abstracts, visit www.arvo.org. For those who have never attended an ARVO meeting, I hope you can do so next year!