A very talented group of researchers, including the world’s best vision scientists and clinicians, assembled in Orlando last month to present their most recent findings on a multitude of topics at the annual ARVO conference. While no single report can encapsulate the thousands of papers presented, here we present 20 intriguing findings involving corneal infections and lid pathology that have especially keen clinical relevance.
The selected abstracts will hopefully help clinicians in general practice, and in particular contact lens practice, better serve our patients.
1. Keratitis and Pseudomonas aeruginosa positivity increase in the summer.
Researchers from SUNY Ophthalmology in Brooklyn analyzed seasonal variations in the incidence of infectious keratitis, as well as seasonal changes in its etiologies, risk factors and clinical outcomes. There is a higher frequency of infectious keratitis and P. aeruginosa positivity during the summer months. Possible contributing factors include warmer temperatures and higher humidity levels.
There should be a heightened awareness to the possibility of corneal infection during warmer seasons—especially in any contact lens wearers.
Program #1507. Seasonal variation as a risk factor for infectious keratitis. ARVO 2014.
2. There is a potential link between corneal innervation and endothelial cell homeostasis.
Boston-based researchers from Harvard’s Massachusetts Eye and Ear Infirmary and the Schepens Eye Research Institute used in vivo confocal microscopy (IVCM) to analyze bilateral corneal endothelial cell density as correlated to sub-basal nerve changes in patients with unilateral stromal scarring due to HSV keratitis. Patients with unilateral HSV keratitis exhibit a significant decrease in corneal endothelial cell density in both the affected eye and the unaffected eye.
Corneal endothelial cell density is correlated with a decrease in corneal sub-basal nerves. As such, the researchers hypothesize a link between corneal innervation and endothelial cell homeostasis.
Program #1471. In vivo confocal microscopy demonstrates bilateral loss of corneal endothelial cells in unilateral herpes simplex. ARVO 2014.
3. AST can regenerate sub-basal nerves.
Another Mass Eye and Ear study evaluated the use of 20% autologous serum tears (AST) in patients with chronic debilitating corneal pain unresponsive to conventional therapy. Using IVCM, underlying alterations of the sub-basal nerve plexus was identified in patients suffering from debilitating corneal neuralgia. AST—rich in neurotrophic factors—lead to corneal sub-basal nerve regeneration and significant improvement in corneal pain in patients with corneal neuropathy.
Nerve beading and presence of neuromas decreased significantly from 37.5% and 75% of all points to 6.25% and 68.75%, respectively.
Program #1468. Efficacy of autologous serum tears for treatment of severe corneal pain in patients with corneal neuropathy: an in vivo confocal microscopy study. ARVO 2014.
4. Bacteria found in contact lens cases could potentially adhere to lenses in the presence of tears.
The degree of contact lens case contamination during use depends on the type of multipurpose disinfecting solution (MPDS) used; certain solutions are associated with high levels of gram-negatives in cases.
Researchers at the School of Optometry and Vision Science at the University of New South Wales, Australia compared adhesion of microbes isolated from these MPDS/lens cases with and without organic soil.
Results indicated that bacteria found in contact lens cases could adhere to contact lenses in relatively high numbers in the presence of organic soil. This might indicate that a similar phenomenon can occur in the presence of tears. This might encourage bacterial transfer from the lens to the cornea and the production of corneal infiltrates.
These particular “bugs” (i.e., Stenotrophomonas maltophilia, Delftia acidovorans and Achromobacter xylosoxidans) have been found in abundance in cases of patients who experience diffuse infiltrative responses while wearing contacts.
Program #4646. Adhesion of stenotrophomonas maltophilia, delftia acidovorans and achromobacter xylosoxidans to contact lenses in the presence of organic soil. ARVO 2014.
5. Peptide melamine-coated contact lenses exhibit high antimicrobial properties.
Investigators at the School of Optometry and Vision Science at the University of New South Wales studied the performance of melamine-coated contact lenses in a human clinical trial. Antimicrobial peptide melamine, applied by covalent bonding onto contact lenses, can produce a broad-spectrum antimicrobial lens.
This study is the first to provide evidence that humans can wear antimicrobial peptide-coated lenses safely. The melamine-coated lens wear was uneventful, with the exception of its association with higher corneal staining in extent and depth.
Following wear, the lenses retained their high antimicrobial activity.
Program #4647. Biocompatibility and retention of activity of melamine antimicrobial contact lenses in a human clinical trial. ARVO 2014.
6. Subtherapeutic dosing of prophylactic antibiotics may increase the likelihood of antibiotic resistance.
Researchers at UPMC, Pittsburgh studied the surveillance cultures of bandage contact lenses (BCL) in patients with a clinical history of requiring a BCL. In analyzing surveillance cultures of BCLs, 84% were culture positive; of these, 24% grew organisms that were resistant to antibiotic treatment.
In 89% of patients, cultures were used to support therapy changes, suggesting that BCL cultures provide useful information for effective prophylaxis—and for guiding treatment if infectious complications arise. Dosing with subtherapeutic prophylactic antibiotic does not seem to lead to increased risk of infection of culture-resistant organisms. However, subtherapeutic dosing may increase the likelihood for an organism becoming resistant to an antibiotic. For this reason it is not recommended that patients with chronic ocular disease use sublethal dosing of prophylactic antibiotics—especially in a population with chronic ocular disease.
Program #4661. Contact lens surveillance cultures in patients wearing bandage contact lenses. ARVO 2014.
7. IL-17A response after infection with Acanthamoeba plays an important role in protecting the host from invading parasites.
In Acanthamoeba keratitis, the relative contribution of a proinflammatory cytokine, IL-17A—which promotes migration, activation and function of neutrophils in the cornea—is poorly defined. The role of adaptive immune response, particularly the contribution of CD4+ T cell subsets such as Th17 and Tregs in AK is yet to be understood.
Acanthamoeba corneal infection induces both Teffector and Treg response, which responds to microbial antigens in the cornea. In contrast to other corneal infections, such as herpes and P. aeruginosa keratitis, where IL-17A exacerbates corneal pathology and inflammation, this study’s findings indicate the IL-17A response after infection with Acanthamoeba plays an important role in protecting the host from invading parasites.
A better understanding of pro-inflammatory cytokine activity in Acanthamoeba keratitis might lead to improved care protocols. Photo: Christine W. Sindt, OD
Perhaps this strategy of antisense therapy will aid in developing more effective treatment options for this dreaded disease process in contact lens wearers.
Program #1689. IL-17A-mediated protection against acanthamoeba keratitis. ARVO 2014.
8. Reservoirs for Acanthamoeba hosts may be more common than we previously thought.
Researchers at Bascom Palmer Eye Institute in Miami investigated the ecological diversity of Acanthamoeba host and associated microbial communities. The team compared clinical isolates from the corneas and contact lenses of patients with Acanthamoeba to associated communities from seven environmental hosts: shower heads, marine waters, swimming pools, ice machines, drinking fountains and eyewash stations.
Acanthamoeba was recovered from all environmental sources and ranged from 11% (pools) to 40% (drinking fountains). Eyewash stations (15.9%) and showerheads (17%) were more frequently associated with Pseudomonas and Mycobacterium species. Reservoirs and transmission niches for Acanthamoeba hosts and associated microbial communities may be more common than previously recognized. Additionally, human colonization and pets may be unrecognized sources.
Program #6260. Ecological diversity of acanthamoeba and associated microbial communities. ARVO 2014.
9. Several bacterial isolates are demonstrating increased antibacterial resistance rates.
The ARMOR (Antibiotic Resistance Monitoring in Ocular MicRoogranisms) surveillance study was initiated in 2009, monitoring resistance trends of bacterial pathogens of ocular significance. A report of the study results to date for 2013, compared to results from 2012, was presented at this year’s ARVO meeting.
Ciprofloxacin and imipenem non-susceptibility rates for P. aeruginosa more than doubled to 14% and 21%, respectively. No resistance was found in H. influenzae isolates. The rate of 6% for non-susceptibility to penicillin remained steady among S. pneumoniae. Azithromycin and imipenem non-susceptibility rates decreased to 29% and 6%, respectively. Slight increases over the previous year were found in isolates of S. aureus and coagulase-negative staphylococci isolates (CoNS) to oxacillin/methicillin (43-59%), ciprofloxacin (33-43%), clindamycin (21%) and azithromycin (60-63%). Multidrug resistance stayed prevalent in S. aureus and CoNS (38-39%) from 2013, especially among methcillin-resistant staphylococci (60-81%).
The 2014 ARMOR surveillance data show increased levels of resistance among previously problematic staphylococci and P. aeruginosa isolates. These results point to judicious use of antibiotics in the treatment of ocular infections, and the need for ongoing studies and surveillance of ocular pathogens.
Program #6281. Antibiotic resistance profile of ocular pathogens — an update from the 2013 us armor surveillance study. ARVO 2014.
10. The antimicrobial activity of tear fluid under a hydrogel contact lens degrades over time.
Contact lens-related corneal infection is common with soft contact lenses, and the risk increases with use of extended wear modalities. This could be due to the lack of tear exchange under soft lenses—tear fluid contains antimicrobial factors. Researchers from UC Berkeley tested the hypothesis that tear fluid between the corneal surface and the contact lens during wear loses the ability to suppress growth of P. aeruginosa over time.
Results of this study show that tear fluid under a hydrogel lens can lose antimicrobial activity with time; packaging solutions can counteract this. It is not clear whether antimicrobial activity is reduced because critical tear components are degraded, excluded or reduced in production. Further study is needed to determine if the effect of packaging solution occurs directly to bacteria or whether it acts indirectly by impacting tear fluid chemistry and physiochemistry.
Program #859. Impact of contact lens wear on post-lens tear fluid antimicrobial activity. ARVO 2014.
11. There may be an indirect link between Demodex folliculorium and chalazia.
Researchers at NYIT College of Osteopathic Medicine, New York Eye and Ear Infirmary and Hofstra Jewish School of Medicine examined the association of Demodex folliculorium and Demodex brevis with chalazia and sought to identify associated histo-pathologic changes. There was a significantly greater mean number of Demodex folliculorum in biopsies with chalazia when compared to biopsies without chalazia, but causality cannot be established between Demodex and chalazia. Their findings suggest that Demodex folliculorium may be indirectly involved in the pathogenesis of chalazia via its effect on the anterior eyelid margin.
Program #6250. Demodex and its association with chalazia: a histopathic study. ARVO 2014.
12. Demodex mites may be associated with dry eye symptoms.
In a study conducted by researchers in private practice in Minnesota and California, patients were examined and asked to fill out four questionnaires: Ocular Surface Disease Index (OSDI), the Subjective Evaluation of Symptom of Dryness (SESoD), the Subjective Evaluation of Frequency of Itch (SEFoI) and the Total Ocular Surface Score (TOSS).
The patients were then examined for the presence of Demodex mites. If any were present, the patient was included in the study.
Average number of mites per patient was 7.93, and 36.1% scored 13 or greater on OSDI and were classified as symptomatic for dry eye. In the SESoD section, 23.6% scored higher than one, indicating clinically significant dryness. In the SEFol section, 20.8% scored higher than one, which signifies clinically significant itching. Finally, in the TOSS score, 27.7% scored higher than 13, a mark that indicates clinically significant itching.
Collarettes around the lashes, a predictable sign of Demodex. Photo: Christine W. Sindt, OD
In all three subsections, the majority of patients presented without symptoms or with minimal symptoms associated with dry eye or allergy. This may help to explain why this condition is often overlooked for treatment.
Program #1996. Symptoms associated with the presence of demodex folliculorum. ARVO 2014.
13. Oral azithromycin seems to be an excellent alternative to oral doxycycline in patients with meibomian gland dysfunction.
Investigators at the Nouvel Hospital Civil De Strasbourg in France studied the clinical efficacy and safety of oral azithromycin vs. oral doxycycline in subjects being treated for MGD. They were also able to evaluate rosacea prevalence in the trial population. Patients with moderate to severe MGD received either oral azithromycin 500mg three times a week tapered for three months or oral doxycycline 100mg daily for three months. Palpebral and dermatologic signs of rosacea were primary outcomes. Secondary measures were quality of life, tear film break-up time, corneal staining, tolerance and compliance.
There was a statistically significant non-inferiority for all endpoints for azithromycin compared to doxyclycine. Only a 5% occurrence of side effects was observed for both groups.
Program #1481. Oral azithromycin versus doxycycline for the treatment of moderate to severe meibomian gland dysfunction (MGD): a randomized prospective non-inferiority study. ARVO 2014.
14. Tearing may help differentiate dry eye from conjunctivochalasis.
Conjuctivochalasis (CCh) causes precorneal tear film instability, increases the mechanical friction during blinking and decreases tear flow in the lower meniscus. Subjective symptoms of CCh vary greatly. Researchers at the Kyoto Prefectural University of Medicine in Kyoto, Japan evaluated the differences in subjective symptoms between CCh and dry eye.
The study involved 87 eyes of 87 dry eye patients. The subjective symptoms—dry eye sensation, difficulty in opening the eye, foreign body sensation, pain, redness, tearing, discharge, itchiness, blurred vision, sensitivity to light, heavy eyelids and eye fatigue—were evaluated by use of the visual analogue scale (VAS). Findings of this study show that CCh exhibits subjective symptoms similar to dry eye.
The symptom of tearing may help differentiate the diagnosis of dry eye from that of CCh; tearing is stronger in CCh secondary to decreased tear flow at the lower tear meniscus due the redundancy of the conjunctiva.
Program #1991. Comparison of subjective symptoms between conjunctivochalasis and dry eye patients. ARVO 2014.
15. Intense pulsed light therapy (IPL) for ocular rosacea can improve dry eye symptoms.
Researchers at the Mayo Clinic in Scottsdale and Arizona College of Medicine in Phoenix conducted a retrospective study to describe the early treatment outcomes for meibomian gland dysfunction and ocular rosacea in dry eye patients with IPL therapy. Medical records of 19 dry eye patients treated monthly with IPL and MG expression were retrospectively examined for outcomes. Demographics, ocular histories, SPEED2 scores, slit-lamp exam and meibomian gland evaluation were reviewed at baseline and after IPL treatment.
The average number of IPL treatments was three. Out of the 19 patients, seven were good responders (≥ 40% decrease in SPEED2), six were mild responders (1% to 39% decrease in SPEED2), five were non-responders or adverse responders (i.e., no change or decrease in SPEED2) and one was intolerant of pain of gland expression. A number of patients noticed transient symptom improvement after the first treatment, including 85.7% of good responders, 66.7% of mild responders and 40% of adverse or non-responders. Additionally, 65.8% of eyes demonstrated improved MGE scores. There were no pathologic changes on slit lamp after therapy.
In this study, 68% of patients had a positive response to IPL. Anecdotal improvement in symptoms after one treatment can be a prognostic indicator of a patient’s responsiveness to IPL. Further work is needed, as this is a small sample and a retrospective study.
Program #2018. Early treatment outcomes in dry eye patients treated with intense pulsed light therapy. ARVO 2014.
16. Androgen treatments significantly influence gene expression in human meibomian gland (HMG) cells and conjunctival epithelial cells.
Androgen insufficiency is considered a significant risk factor for development of MGD. To better understand why this is so, researchers at Australia’s University of New South Wales and the Houston College of Optometry sought to determine the effect of two androgens—testosterone and dehuydroephiandrosterone—on HMG cell proliferation and lipid production.
Androgens increased cell proliferation and lipid production for up to 24 hours in HMG cells, but the long-term effect of androgen on cell proliferation and lipid production needs further study. The findings of this study may be useful in the development of androgen based topical therapy for MGD treatment.
Program #18 Poster Board #A0006. The effect of androgens on human meibomian gland epithelial cells. ARVO 2014.
17. Microorganisms in cataract patients with MGD may contaminate the incision.
In a study conducted at the Bejing University Third Hospita, the influence of meibomian gland excreta on cataract surgery was evaluated. Sixty cataract patients with dry eye were treated with meibomian gland massage and the secretions were collected for bacterial culture, fungal culture and antibiotic drug sensitivity test. Among the 60 eyes for bacterial culture were 48 positive results, in which 46 were gram-positive and two were gram-negative. There was a 3% positive result for fungal culture.
The conclusions drawn from this study suggest there is microorganism growth in meibomian glands of some cataract patients who have MGD, which has a chance to contaminate the surgical incision. Researchers consider the intraocular surgery incision as a type-11 incision. The orifice of the meibomian gland should be completely wrapped to better prevent intra- or postoperative infection.
Program #48 Poster Board #A0036. Detection of microorganisms in meibomian glands of cataract surgical patients. ARVO 2014.
18. Obstructive sleep apnea-hypopnia syndrome (OSAHS) is associated with a number of conditions.
Floppy eyelid syndrome (FES) is a subset of lax eyelid conditions characterized by an extreme laxity of the upper eyelids. This causes eversion upon minimal mechanical manipulation. FES is known to be associated with ocular and systemic disease, including OSAHS. Researchers at Loyola University of Chicago conducted a study to determine the association of OSAHS with various ocular and systemic diseases.
A data mining study for ocular and systemic disease was performed using the electronic database of 562,585 patients. The study demonstrates a positive association between OSAHS and several ocular diseases: FES, dry eye, rosacea conjunctivitis and kerotoconus. Systemic associations include obesity, hypertension, rosacea and diabetes mellitus type 1 and 2. The association between FES and ASOHS is significant, but the researcher’s data suggests it is underdiagnosed at this medical center compared to control values in the literature.
Program #1465 Poster Board #C0104. The association of systemic and ocular disease and the underdiagnosis of floppy eyelid syndrome in patients with OSA. ARVO 2014.
19. Glaucoma drugs have a negative effect on both meibomian gland morphology and function.
Researchers from Pamplona, Spain sought to determine the impact of topical glaucoma meds on the meibomian glands. This was a cross-sectional, observational study of 45 patients treated with glacuoma drops and 20 without any topical therapy. Those treated underwent therapy for more than one year. Researchers quantified the number of treatments used, eye drops instilled per day and medications that contained benzalkonium chloride.
The following tests were performed: Schrimer test, tear break-up time test, slit-lamp biomicroscopy analysis of the ocular surface and non-contact meibography of the upper eyelid. The results suggest that topical glaucoma treatments affect the meibomian gland morphology (specifically, tortuosity and length) and function. They also decrease the total area of meibomian glands in the upper eyelid.
Program #1487 Poster Board #C0126. Evaluation of meibomian gland morphology and function in patients treated with anti-glaucomatous eye drops. ARVO 2014.
20. Contact lens wear is associated with long-term negative changes to both the tear film and meibomian gland function.
In another study out of the University of New South Wales, researchers investigated the characteristics of the meibomian glands (MG) and tear film in current and former contact lens wearers compared to non-wearers.
This was an ongoing, cross-sectional study with 74 participants. Procedures were conducted to investigate symptoms of dry eye, function of MGs and tear film, lipid layer thickness, phenol red thread, tear meniscus cross-sectional area, tear osmolarity, tear evaporation rate and lid wiper staining, and morphology of MGs.
The study showed that contact lens wear is associated with negative changes to the tear film (e.g., osmolarity and tear break-up time), as well as MG function and morphology. Even after discontinuing lens wear for six months, the changes appear to persist for some.
Program #6065 Poster Board #A0142. Impact of current and previous contact lens wear on meibomian glands and tear film characteristics. ARVO 2014.