Friday, January 11, 2008

Study: A veritable rainbow of corneal staining

I've been wondering when we'd start seeing more studies on staining methods. Seems like I've read a ton of little newspaper snippets over the last several months about lissamine green from some kind of press release out of UTSW. Anyway, this study is basically mixing and matching different dyes for different types of staining to see if they can make the process simpler without losing any diagnostic accuracy.

An evaluation of the efficacy of fluorescein, rose bengal, lissamine green, and a new dye mixture for ocular surface staining.
Korb DR, Herman JP, Finnemore VM, Exford JM, Blackie CA
Eye Contact Lens. 2008 Jan;34(1):61-4

PURPOSE.: Sodium fluorescein is considered the premier dye for corneal staining and, similarly, rose bengal (RB) for conjunctival staining. A mixture of 1% fluorescein and 1% rose bengal has been reported as advantageous in daily practice. Mixtures of lissamine green with other ocular stains have not been reported. The purposes of this study were to review the clinical staining characteristics of fluorescein, rose bengal, and lissamine green in controlled dose and concentration and determine whether optimal staining of the cornea and bulbar conjunctiva are possible by using dye mixtures.
METHODS.: Sixteen 10-muL solutions of fluorescein, rose bengal, lissamine green, and their mixtures were evaluated. Fourteen subjects with a diagnosis of dry eye were tested for staining with various combinations of the dyes. Examination of staining was made by using standard clinical practices.
RESULTS.: A mixture of 2% fluorescein and 1% rose bengal was the most efficacious staining mixture for the cornea and conjunctiva, but moderate to marked discomfort was reported. The mixture of 2% fluorescein and 1% lissamine green did not result in discomfort and provided optimal corneal and conjunctival staining with only slightly less efficacy than 2% fluorescein and 1% rose bengal; 2% and 3% lissamine green produced burning and discomfort. The fluorescent characteristics of fluorescein were not significantly altered by the addition of 1% lissamine green. The preferred mixture for simultaneous and efficacious staining of the cornea and conjunctiva without an adverse sensation was 2% fluorescein and 1% lissamine green.
CONCLUSIONS.: A mixture of 2% fluorescein and 1% lissamine green offers excellent simultaneous corneal and bulbar conjunctival staining and could replace the use of individual dyes for ocular staining and contact lens practice.

Study: Restasis and contacts

In this interesting study, completed in Birmingham (as opposed to, er, Irvine), contact lens wearers with dry eye issues experienced NO benefit to signs OR symptoms of dry eye after taking Restasis for three months. Not one measly little parameter showed any statistically significant improvement.

The abstract does not tell us how many participants there were, and the authors are conscientious about acknowledging that the "small sample size" may have affected the results. Not that they ought to feel obliged to be apologetic about not reporting better results! But seriously, it is not easy to go against the grain of published literature, which is overwhelmingly pro Restasis.

While this study is "about" contact lens wearers, note that it was NOT attempting to measure their contact lens comfort. It was measuring their dry eye signs and symptoms. It kind of struck me as a subtle back door way of really saying, "Here's a broad spectrum group of people for whom Restasis did nothing". The more obvious message of the study, of course, is that all those physicians who refuse to stray from the path of pharmacological treatment for ocular surface disease even where other treatment is clearly indicated by lid margin disease, nocturnal lagophthalmos, BAK toxicity or what have you, not to mention chronic contact lens overwear, should not look to Restasis as the magic bullet for contact lens tolerance problems. Not that I hold out hope of that message taking hold, mind you. After all, this is an industry that indirectly touts laser refractive surgeries as a solution for contact lens intolerance. Sigh.

Efficacy of Cyclosporine 0.05% Ophthalmic Emulsion in Contact Lens Wearers With Dry Eyes.
Willen CM, McGwin G, Liu B, Owsley C, Rosenstiel C
Eye Contact Lens. 2008 Jan;34(1):43-45

PURPOSE.: To assess the efficacy of cyclosporine 0.05% ophthalmic emulsion (Restasis; Allergan, Inc., Irvine, CA) in the treatment of contact lens wearers with dry eyes.

METHODS.: Contact lens wearers citing dry eye problems were identified through chart review. Participants were randomly assigned to a treatment group, receiving vials of cyclosporine 0.05% ophthalmic emulsion to use twice daily, or a placebo group, receiving vials of rewetting drops (Refresh Preservative Free Artificial Tears; Allergan, Inc.) to use twice daily. Corneal staining, tear film breakup time, and Schirmer test results were documented at baseline and after 3 months. Participants also completed questionnaires, the Ocular Surface Disease Index, and the National Eye Institute Refractive Error Quality of Life Instrument at baseline and after 3 months.

RESULTS.: For all parameters, including objective findings and subjective reporting of symptoms, there was no statistically significant difference between the treatment and placebo groups.

CONCLUSIONS.: This study did not detect a beneficial effect in using cyclosporine 0.05% ophthalmic emulsion over rewetting drops for contact lens wearers. This may be attributable to the small sample size. It is also possible that the mechanism of the dry eye state in contact lens wearers may be different from that of other dry eye states and thus make cyclosporine 0.05% ophthalmic emulsion an ineffective treatment.

Study: 02Optix lenses

To be taken with just as large a clump of salt as any manufacturer-funded study, but for those interested in any claims of dry eye friendly contact lenses, read on.

Performance of Lotrafilcon B silicone hydrogel contact lenses in experienced low-Dk/t daily lens wearers
Dillehay SM, Miller MB
Eye Contact Lens. 2007 Nov;33(6 Pt 1):272-7

PURPOSE: The silicone hydrogel lens O2OPTIX with a Dk/t of 138 (at -3.00 diopters [D]) was evaluated and compared with patients' habitual low-Dk/t lenses.
METHODS: This large, multisite (United States and Canada), single-masked study enrolled experienced daily-wear, low-Dk/t, 2-week replacement soft contact lens wearers. Subjects underwent baseline evaluations and were fitted with O2OPTIX lenses for a 2-week period. After 2 weeks, subjects returned for assessment versus their habitual lenses.
RESULTS: Data for 760 subjects were analyzed. The overall average habitual contact lens power was -3.13 D, and the average O2OPTIX lens power was -3.22 D. Biomicroscopy evaluations showed improvements in signs related to corneal health with O2OPTIX. Conjunctival and limbal redness, corneal neovascularization, corneal edema, and corneal and conjunctival staining all decreased significantly from baseline. O2OPTIX lenses performed better than habitual lenses in terms of comfort, symptoms, and overall preference. When wearing O2OPTIX lenses, significantly fewer subjects reported problems compared to their habitual lenses, including uncomfortable lens wear (-20.3%), redness (-44.5%), dryness during the day (-40.2%), and dryness at the end of the day (-34.4%); 47.9% reported that they could wear O2OPTIX lenses longer than their habitual lenses. At the end of study, among those with a preference, a significantly greater proportion of patients (60.3%) preferred O2OPTIX lenses to their habitual lenses.
CONCLUSIONS: Daily wear of O2OPTIX lenses resulted in improvements in corneal signs of health and patient symptoms and provided excellent vision and comfort. O2OPTIX lenses were preferred by subjects over their habitual lenses.

Case report: From Osteopoikilosis to RA to dry eye

Just a tiny case report in a rheumatology journal but I thought it was an interesting reminder of the challenging detective work occasionally needed to track down the source of dry eye symptoms.

Osteopoikilosis in a patient with rheumatoid arthritis complicated with dry eyes.
Ureten K
Rheumatol Int. 2007 Sep;27(11):1079-82. Epub 2007 Mar 29

Osteopoikilosis is an uncommon sclerosing bone dysplasia of unknown etiology. It is usually detected as a coincidental finding at radiographic examination. Mild joint pain and swelling may be seen in 15-20% of cases. Osteopoikilosis is rarely associated with rheumatoid arthritis. In this case report a young man with osteopoikilosis who was diagnosed as having rheumatoid arthritis complicated with dry eyes is presented. Although patients with osteopoikilosis may have articular symptoms, those patients should be carefully examined for a possible association with a rheumatic condition

Monday, January 7, 2008

Study: Pre-operative risk factors for post LASIK dry eye

To those of you with post LASIK dry eye, your initial response will probably be "Well, duh! Dry before surgery = drier / higher risk afterwards. Oh and by the way, why didn't they run those tests on ME before surgery?" Fair enough, it's not exactly a newsworthy study. However, there are one or two points of interest. Check out the one I highlighted in the abstract, for example....

On the other hand, what I really want to know is, why didn't they do an anesthetized schirmer - or if they did, why not report on it? (Hard to believe it's because it correlated with nothing at all.) LASIK surgeons do not normally relish operating on the likes of Sjogrens patients, and most of us lasikees were not seriously aqueous deficient before lasik. MGD red flags is what we had.

Oh - and another point of mild interest. Those of you who gripe about being told repeatedly that you're still healing may be interested to note that these authors consider dry at 9 months to be "chronic" dryness. Sounds discouraging on the face of it but when you put this in the context of all the other studies showing nerve regrowth for far longer periods, I would not take it too seriously.

Preoperative characteristics and a potential mechanism of chronic dry eye after LASIK.
Konomi K, Chen LL, Tarko RS, Scally A, Schaumberg DA, Azar D, Dartt DA
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):168-74

PURPOSE: To determine whether measurable preoperative characteristics predispose patients to chronic dry eye after laser in situ keratomileusis (LASIK).

METHODS: The study consisted of 24 eyes of 24 patients who underwent LASIK. Tear breakup time, Schirmer testing with and without anesthesia, rose bengal staining, central corneal sensitivity, nucleus-to-cytoplasmic ratio, and goblet cell density were evaluated 2 weeks before and 1 week, 3 months, and 9 months after surgery. Patients were classified into two outcome groups, the nondry-eye group (NDEG) and the chronic dry-eye group (CDEG), on the basis of dry eye status 9 months after surgery. The authors tested whether preoperative values of each parameter were associated with the development of chronic dry eye.

RESULTS: All parameters, except rose bengal staining, deteriorated significantly after surgery but returned to preoperative levels within 3 to 9 months. The CDEG had significantly lower preoperative Schirmer test values with and without anesthesia and were delayed in recovery after surgery in goblet cell density, rose bengal staining, Schirmer test values without anesthesia, and tear breakup time. Results of preoperative Schirmer tests without anesthesia positively correlated with tear breakup time 9 months after surgery.

CONCLUSIONS: Preoperative tear volume may affect recovery of the ocular surface after LASIK and may increase the risk for chronic dry eye

Study: More on mucins

Well, I wish I could wave a magic wand over this to translate it to normal English. On the other hand, those of you who, like me, are interested in the mucin aspects of dry eye mostly know so much more about it than I do that I really don't have to bother :-) For those who don't know why they should care, mucin is the sticky substance on the surface of the cornea that makes tears adhere properly to the surface of the eye. With or without a good tear production or tear quality, the state of your mucin "layer" can make a big difference to your comfort and ocular surface health. That is why this area of research is so critical in the long-term.

Antiadhesive Character of Mucin O-glycans at the Apical Surface of Corneal Epithelial Cells.
Sumiyoshi M, Ricciuto J, Tisdale A, Gipson IK, Mantelli F, Arg├╝eso P.
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):197-203.

PURPOSE: Prolonged contact of opposite mucosal surfaces, which occurs on the ocular surface, oral cavity, reproductive tract, and gut, requires a specialized apical cell surface that prevents adhesion. The purpose of this study was to evaluate the contribution of mucin O-glycans to the antiadhesive character of human corneal-limbal epithelial (HCLE) cells.
METHODS: Mucin O-glycan biosynthesis in HCLE cells was disrupted by metabolic interference with benzyl-alpha-GalNAc. The cell surface mucin MUC16 and its carbohydrate epitope H185 were detected by immunofluorescence and Western blot. HCLE cell surface features were assessed by field emission scanning electron microscopy. Cell-cell adhesion assays were performed under static conditions and in a parallel plate laminar flow chamber.
RESULTS: Benzyl-alpha-GalNAc disrupted the biosynthesis of O-glycans without affecting apomucin biosynthesis or cell surface morphology. Static adhesion assays showed that the apical surface of differentiated HCLE cells expressing MUC16 and H185 was more antiadhesive than undifferentiated HCLE cells, which lacked MUC16. Abrogation of mucin O-glycosylation in differentiated cultures with benzyl-alpha-GalNAc resulted in increased adhesion of applied corneal epithelial cells and corneal fibroblasts. The antiadhesive effect of mucin O-glycans was further demonstrated by fluorescence video microscopy in dynamic flow adhesion assays. Cationized ferritin labeling of the cell surface indicated that anionic repulsion did not contribute to the antiadhesive character of the apical surface.
CONCLUSIONS: These results indicate that epithelial O-glycans contribute to the antiadhesive properties of cell surface-associated mucins in corneal epithelial cells and suggest that alterations in mucin O-glycosylation are involved in the pathology of drying mucosal diseases (e.g., dry eye).

Study: Systane (literature review)

Dr. Foulks had a review of Systane published recently. Nothing earth-shattering in the abstract, basically the easily believable notion that "It's better than several other drops out there".

Clinical evaluation of the efficacy of PEG/PG lubricant eye drops with gelling agent (HP-Guar) for the relief of the signs and symptoms of dry eye disease: A review.

Foulks GN.
Drugs Today (Barc). 2007 Dec;43(12):887-96

The objective of this review is to evaluate the efficacy of polyethylene glycol (PEG) 400/propylen glycol (PG) in-situ gellable lubricant eye drops with HP-Guar (as the gelling agent) in reducing dry eye signs and symptom. A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry eye disease and in-situ PEG/PG gellable lubricant eye drops. The search covered the period prior to July 2007. Articles were selected based on their direct applicability to the subject matter. A manual search was also conducted based on citations in the published literature. Additional original reports were referenced at the author's discretion if deemed applicable to the subject matter of the review. Forty-three (43) articles were identified and are reviewed here. The published literature indicated that dry eye disease is a prevalent condition in the United States, especially among women and the elderly. The biphasic mechanism of action of in-situ PEG/PG gellable lubricant eye drops, afforded by their unique structure, renders them more effective at reducing the signs and symptoms of dry eye than many commercially available over-the-counter products. (c) 2007 Prous Science. All rights reserved.

Newsblurb: Autologous serum

While autologous serum certainly can't be considered a new breakthrough, I'm encouraged to see a little popular press about it to spread the word. Also this is a heads up to folks in the midwest for another dr. with experience in using serum drops.

St. John’s doctor uses 'breakthrough' eye drops to treat severe dryness

St. John’s Clinic ophthalmologist Dr. Shachar Tauber has begun using what he calls “a breakthrough alternative” in the treatment of patients with severe dry eye.

Autologous serum drops are eye drops are made from the patient’s own blood, he said....

“We use these drops in intervals for patients who have shingles and who have had Lasik and PRK procedures,” Tauber said. “We don’t know what chemical it is exactly in blood that has the healing property; we think it’s the combination of proteins such as albumin and insulin, and the body’s stem cells. They all work in concert to promote healing in the eyes when nothing else helps.”

Tauber has treated about 50 patients who have severe dry eye with autologous serum drops. Patients often have eyes that are very swollen and inflamed most of the times and no eye drops seem to help, he said. Some are in severe pain and can’t keep their eyes open....