Abstract: LASIK and the ocular surface

Nice succinct summary of the major ocular surface complications LASIK can present. Note in particular the reference to RCE happening to people who already had a poorly adhering epithelium. This is one of the reasons that if you're going to get laser surgery, you need to be evaluated really, really thoroughly by a specialist first... Mild ABMD is not obvious, and I know plenty of people who did not have it diagnosed before LASIK... and in a few cases, the first thing that caused them to learn about it was when their epithelium sloughed off after surgery. (By the way, that hurts. A lot.)

LASIK and the ocular surface.
Cornea. 2008 Sep;27 Suppl 1:S70-6.
Toda I.

Wound healing after LASIK sometimes compromises homeostasis of the ocular surface. Diffuse lamellar keratitis is a post-LASIK inflammatory condition in the interface that appears during the first week after LASIK. The etiology of diffuse lamellar keratitis is unknown, but the association with allergic reaction to detergent, bacteria, and other chemicals is suspected. The condition is mostly self-limiting. Topical and/or oral corticosteroids may be effective against stage 2 disease, whereas flap lift and irrigation might be required in stage 3. Epithelial ingrowth occurs in about 1% of LASIK eyes. Although most cases heal spontaneously, some require surgical removal. There are 2 known mechanisms for epithelial ingrowth: epithelial invasion and epithelial implantation. Epithelial invasion grows in 2 distinct ways--outside invasion and flap epithelial invasion. The latter type is often seen after enhancement and may be treatment resistant. Patients with compromised attachment of corneal epithelium before LASIK may develop recurrent corneal erosion, which sometimes requires phototherapeutic keratectomy. Subepithelial opacity after viral infection, even long after infection, often recurs after LASIK and affects refraction and visual acuity. Topical corticosteroid may be effective to prevent recurrence. Dry eye is a common complication after LASIK. Although post-LASIK dry eye is usually temporary, some patients complain of severe symptoms that may negatively influence their satisfaction with the outcome. For example, functional visual acuity significantly decreases after LASIK. The possible mechanisms for post-LASIK dry eye may be associated with loss of neurotrophic effect, damage of goblet cells, and altered corneal shape.

Some of you whose lives have been turned upside down for a couple of years by severe post LASIK dry eye might get a giggle out of this understatement from the abstract:

Although post-LASIK dry eye is usually temporary, some patients complain of severe symptoms that may negatively influence their satisfaction with the outcome.

For the laypeople reading this, don't forget "usually" can mean anywhere between 51% on up (and doctors, before you're tempted to tell me I'm overdramatizing things, go back and read the published studies that showed between 15 and 36% of patients having unresolved dry eye 6 months after surgery).

And any doctor that is surprised 24/7 pain can make you dissatisfied with an elective surgery, please raise your hand (grin).

DRY EYE CONFERENCE March 7, 2009

On Saturday, March 7, 2009 the Sjogrens Syndrome Foundation will be hosting a one-day dry eye conference at the Marriott in Long Beach, California. There will be several doctors speaking, including SSF board chairman Gary Foulks MD, and there will be several companies exhibiting.

All dry eye topics will be covered (not just Sjogrens) and all dry eye patients are welcome to attend!

We don't have anything settled yet but... we'll definitely be having some kind of DryEyeZone social get-together that weekend, Friday or Saturday evening (or both).

More details will be posted here and on DryEyeTalk after the program is finalized. I'll also have brochures available.

Abstract: Signs vs. symptoms in Sjogrens patients

Hmph. I thought I had already reported on this but can't find it on the blog so I guess I didn't.

Basically just tells us... as we know... that the correlation between dry eye signs and symptoms is poor even for Sjogrens Syndrome patients, and suggests that reduced corneal sensitivity is part of the explanation.

[Correlation between signals and symptoms of dry eye in Sjögren's syndrome patients]
Arq Bras Oftalmol. 2008 Jul-Aug;71(4):547-52.
[Article in Portuguese]

Barboza MN, Barboza GN, de Melo GM, Sato E, Dantas MC, Dantas PE, Felberg S.

PURPOSE: To study the correlation between the signals and symptoms of dry eye in Sjögren's syndrome patients.

METHODS: We formed the case group with 17 Sjögren's syndrome patients and the control group with 25 normal patients. For evaluation of the symptoms the "Ocular Surface Disease Index (OSDI)" questionnaire was applied to both groups and, after that, all the individuals were submitted to the ocular tests: Schirmer I and II, coloration of the ocular surface with rose bengal, pachymetry and esthesiometry. Spearman's correlation test was used to analyze the correlations between signals and symptoms and Student's t test for independent samples was used for comparison of the averages of the values found by the "Ocular Surface Disease Index (OSDI)" questionnaire and the ocular tests between the patients of the groups.

RESULTS: This study had evidenced a weak correlation between "Ocular Surface Disease Index (OSDI)" symptoms and ocular tests, which it indicates that not all the patients who presented exuberant symptoms, showed proportionally modified tests. The cornea sensitivity of the case group was reduced when compared with that of the control group. All the studied parameters in the case group presented significant differences (p<0.05) when compared with the control group.

CONCLUSION: There was a weak correlation between Sjögren's syndrome patients' ocular symptoms and signals that indicate the severity of the illness. The variation of cornea sensitivity found in the Sjögren's syndrome patient group may be one of the responsible factors for this weak correlation. All the studied parameters were significantly modified in the Sjögren's syndrome patients group when compared with those found in the control group.

Abstract: Autologous serum (again)

While talking recently with a lady with severe post PRK dry eye who had recently sought (yet) another opinion from a well reputed corneal specialist, I was rather disgusted to hear that the doctor stated flatly that she does not ever use autologous serum because "it doesn't work". Hm. News to me. There has been a plethora of studies about it in the last couple of years - clearly it's helping at least enough people to fill a lot of studies and it does not deserve the big brush-off from ophthalmologists, especially if they have been unable to resolve their patients' symptoms in other ways.

Incidentally, the same doctor professed not to believe that PRK can cause dry eye or that LASIK can cause persistent dry eye. What is wrong with these people? Have they drunk too much pharmaceutical kool-aid, or don't they read their own peers' published studies at least once in awhile?

Autologous serum eye drops for the treatment of dry eye diseases.
Cornea. 2008 Sep;27 Suppl 1:S25-30.

Kojima T, Higuchi A, Goto E, Matsumoto Y, Dogru M, Tsubota K.
Department of Ophthalmology, Social Insurance Chukyo Hospital, Nagoya, Japan. tkojkoj@mac.com

Conventional treatment of dry eye mainly consists of the use of preservative-free artificial eye drops and punctal occlusion. None of the commercially available artificial tear preparations include essential tear components such as epidermal growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor, and vitamin A-all of which have been shown to play important roles in the maintenance of a healthy ocular surface epithelial milieu. We reported previously that autologous serum (AS) eye drops contain these essential factors and that AS eye drops are beneficial in the treatment of ocular surface diseases such as persistent epithelial defects, superior limbic keratoconjunctivitis, keratoconjunctivitis sicca, and neurotrophic keratopathy. However, there is some controversy regarding the efficacy of AS treatment. We demonstrated that this modality is more effective than artificial tears in a randomized control study. In in vivo and in vitro experiments, AS eye drops showed marked suppression of apoptosis in the conjunctival and corneal epithelium. Albumin, the major protein in serum, improved ocular surface damage in vivo and rescued apoptosis after serum deprivation in vitro. The biological background of AS eye drops and previous clinical studies of these medications for the treatment of dry eye are discussed.

Abstract: Tear film biomarkers

Compositional Profiling and Biomarker Identification of the Tear Film.
Ocul Surf. 2008 Oct;6(4):175-185.
Jacob JT, Ham B.

ABSTRACT Identification of tear film proteins and lipids is important for the elucidation of contact lens incompatibilities, tear film instabilities, dry eye syndromes, and other eye diseases. Compositional analysis of the tear film has been hampered in the past by the complex nature of the fluid and small sample size. Previously, all analytical methods required pooling of tear samples and molecular manipulation for detection of proteins and lipids, all of which skewed the resultant data. With the advent of nanoscale detection and analysis methods, it has become possible to identify specific tear components. This paper reviews the recent advances in tear sampling, proteomics, and lipidomics. Compositional profiling techniques, such as multi-dimensional electrophoresis, high performance liquid chromatography, and mass spectrometry, are assessed. Application of these techniques to identify potential biomarkers for specific tear disease conditions, such as blepharitis and dry eye, are evaluated.

I finally strained the budget and renewed my subscription to The Ocular Surface.... nice to be able to read the whole thing agin. This article is an in-depth review of advances in understanding tear film composition better.

For those of you who wonder why there isn't a "cure" for dry eye yet... thought you might be interested in this statement from the article's introduction, showing just how far we have to go on understanding the tear film itself, lot alone how to fix it:

...We currently have very little definitive information regarding which specific elements change in response to glandular disease or environmental issues. Nor do we know the concentrations of these elements that can induce physiological changes in the tear film. Although the signs and symptoms of tear film instability have been fairly well characterized, the specific etiology and physiological changes responsible for that instability are not well known.

Abstract: More on Lacritin

Some of the DEZ old-timers will remember when we first came across Lacritin. Here's a newly released study about it. I didn't realize that it could have implications for blepharitis too.

Exp Eye Res. 2008 Sep 18.
Lacritin and other new proteins of the lacrimal functional unit.
McKown RL, Wang N, Raab RW, Karnati R, Zhang Y, Williams PB, Laurie GW.

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

I was thinking this was the first published study on lacritin in ocular surface research but I found one other on Medline that I must have missed last year:

Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes.

OSN discussion on blepharitis treatments

Ocular Surgery News ran an interesting discussion amongst seveal ophthalmologists about treatments for blepharitis. In some cases the differences in views about what treatments to start with is quite striking.

Physicians examine treatment options for patient with blepharitis

COMPRESSES
I was pleased to see general agreement about the importance of warm compresses... but I wonder how much attention any of them are paying to methods and ensuring their patients get compresses that are conducive to compliance.

PLUGS
The usual "cesspool" talk about premature insertion of plugs when there is active blepharitis.

ORAL ANTIBIOTICS
There was some discussion about longterm use of doxy etc. Dr. Slonim compares doxycycline, minocycline and tetracycline. Clearly the frequency with which these antibiotics are prescribed has decreased since the study came out linking them to increased breast cancer risk in women, though Dr. MacDonald (whose regimen sounded like the most Rx-heavy amongst them incidentally) points out:

That study revealed an apparent relationship between oral antibiotic use and breast cancer in women; the results initially panicked everyone. You have to tell patients in advance that the one exception was the group of women on macrolide and tetracycline antibiotics for skin and dermatological/external disease conditions — there was no correlation. So you have to point that out to them in advance because your patients will find the study, and they will call you the next day about it.

TOPICAL ANTIBIOTICS and STEROIDS
Quite a range of opinions, from Dr. Slonim who routinely prescribes them to Dr. Raizman, who minimizes emphasis on drugs in general because of the chronic nature of the condition... rather, his focus is on heat and omega 3s as standard treatment:

I think just about every patient should be using hot compresses. That is easy and safe. If you see terrible meibomian gland obstruction, those patients need doxycycline, minocycline or tetracycline.

Most patients are much more mild. You start to talk to them about antibiotics, and right away they are worried about taking a chronic antibiotic therapy, and justifiably so. And now we have good data to support the use of oils taken orally that are quite helpful for the mild to moderate cases of meibomian gland disease. So I’ll have patients take flax or fish oil, about 2,000 mg a day. I do not think it is critical to focus on one particular type of oil. I think patients get benefits from using any of these products, but that would be my second line of treatment.

I like to avoid steroids. This is a chronic disease. Yes, you can clear them up temporarily. None of us want our patients on steroids for blepharitis for months or years, so I will use them for an occasional flare-up, but I like to stay away from that.

I do not find Restasis to be especially helpful. Occasionally, some patients will get benefit from it, but that is definitely low on my list of treatments, as are topical antibiotics to the lid margins. I do not find that to be as effective, either. So using that combination of strategies, more or less in that order, I get good results on the majority of my patients.

Abstract: Dry eye risks from microsurgery on tumor patients

Facial Nerve Function Insufficiency after Radiosurgery versus Microsurgery.Prog Neurol Surg. 2008;21:108-18.
Tamura M, Murata N, Hayashi M, Roche PH, Régis J.

Background: Due to the synergic role of the facial nerve and the nervus intermedius in the mechanical protection of the eye and taste, vestibular schwannomas and/or their treatment may prove to be dangerous for the visual function and taste. Our goal was to evaluate and compare the impact of the tumor itself and the impact of microsurgery (MS) or Gamma Knife radiosurgery (GKS).

Materials and Methods: A functional questionnaire evaluating, among other items, patient complaints related to the eye and taste has been given out to a series of 200 patients 3 years after the GKS of a unilateral vestibular schwannoma not previously resected. Their answers were compared with those of a group of 200 patients operated on microsurgically. A Schirmer test was additionally performed before radiosurgery (RS) and more than 2 years after RS in 66 patients.

Results: The risk of dry eye and burning eye is much higher in patients operated by MS compared to patients operated by GKS due to the high incidence of facial palsy (FP) in the former (57/99) and its absence in the later (0/80). In the population operated on microsurgically, the presence of a permanent FP (57 patients among 99 responding to the questionnaire) was, of course, associated with a high rate of complaint, with burning eye in 27 and crying eye in 39. In patients from the two arms with no FP, a dry eye was reported in 8/64 after GKS and 7/42 after MS (not significant) and a burning eye in 9/64 after GKS and 9/42 after MS (not significant). Thus, 14% of patients with no clinical signs of impairment of the VIIth motor nerve presented signs indicating the injury of the intermedius nerve, with the same probability whatever the kind of surgery. When no permanent FP was observed, a crocodile tear syndrome was more frequently observed after MS (4/42 versus 1/64; p = 0.07). This suggests an early lesion of the VIIth motor nerve and nervus intermedius and a subsequent abnormal regrowth. The only patient reporting a crocodile tear syndrome after GKS turned out to have a transiently presented mild deficit of the orbicular muscle signing a transient partial facial nerve injury. In the absence of FP, a 'crying eye' was reported more frequently after MS (16/42 vs. 9/64; p = 0.01) leading us to suspect a frequent subclinical injury of the VIIth nerve in those patients operated on using MS with no obvious FP. Patients tested with the Schirmer test before and more than 2 years later were improved in 27.3%, stable in 56.1% and worse in 16.7% of cases. The answers about taste showed that 8.1% of patients after GKS and 45.5% of patients after MS complained of taste.

Conclusions: This study is the first demonstrating that RS can induce nervus intermedius injury in a small percentage of cases (14%). These patients have been treated 11 years ago with what we can consider as 'archeo-GKS technology' compared to today's radiosurgical instruments. Influence of modern GKS on the nervus intermedius is currently under evaluation in our group. However, symptoms related to the eye and taste either due to the injury of the nervus intermedius or the VIIth motor nerve or both are much more frequent after MS than after RS.

Drug news: The latest on Prolacria

Inspire is asking the FDA for a special protocol assessment for their plans for their latest phase III trial.

Inspire initiates special protocol assessment process for dry eye trial

Sep 25, 2008 (Datamonitor via COMTEX) -- Inspire Pharmaceuticals, a biopharmaceutical company, has submitted a clinical protocol and request for special protocol assessment to the FDA for a pivotal Phase III environmental trial with Prolacria for the treatment of dry eye disease.

The protocol is based on information from a detailed analysis of the overall Prolacria clinical trial data to date, including Inspire's Phase III trials and recently completed pilot trial, and consultation with the FDA, Allergan, Inspire's corporate partner, and other dry eye experts.

After detailed analysis, Inspire determined that designing and conducting a further environmental trial was a more appropriate course than further studies of Prolacria in a controlled adverse environment.

Abstract: How the tear film thins and breaks up

Is it, or is it not evaporation... methinks this is a subject Dr. Holly has gone into at some length... Aha! Here it is. Very interesting discussion.

Contributions of evaporation and other mechanisms to tear film thinning and break-up.
Optom Vis Sci. 2008 Aug;85(8):623-30. Links
King-Smith PE, Nichols JJ, Nichols KK, Fink BA, Braun RJ.

PURPOSE: To evaluate the contribution of three mechanisms-evaporation of the tear film, inward flow of water into the corneal epithelium or contact lens, and "tangential flow" along the surface of epithelium or contact lens-to the thinning of the tear film between blinks and to tear film break-up. In addition to a discussion of relevant studies, some previously unpublished images are presented illustrating aspects of tear film break-up.

CONTRIBUTIONS OF THREE MECHANISMS TO TEAR FILM BREAK-UP: Inward flow of water into the epithelium or contact lens is probably unimportant, and a small flow in the opposite direction may actually occur. Tangential flow is probably important in certain special cases of tear film break-up-at the black line near the tear meniscus, over surface elevations, after partial blinks, and from small thick lipid spots in the tear film. In all these special cases it is argued that tangential flow is important initially, but evaporation may be needed for final thinning to break-up. It is argued that most of the observed tear film thinning between blinks is due to evaporation, rather than tangential flow, and that large "pool" break-up regions are the result of evaporation over an extended area.

CONCLUSION: Evaporation in our "free-air" conditions may be four to five times faster than the average of the values reported in the literature when air currents are prevented by preocular chambers. However, recent evaporation measurements using "ventilated chambers" give higher values, which may correspond better to free-air conditions. Thus evaporation may be fast enough to explain many cases of tear film break-up, and to give rise to considerable increases in the local osmolarity of the tear film between blinks.

Abstract: Lubricants and lenses

A little study comparing contact lens comfort after 6 hours wear if no lubricant was used, saline, or an OTC lubricating drop. Bottom line - type of lens matters more than what lubricant is used.

Lubricant effects on low Dk and silicone hydrogel lens comfort.
Optom Vis Sci. 2008 Aug;85(8):773-7.
Ozkan J, Papas E.

PURPOSE: To investigate the influence of three lubricants of varying viscosity, on postinsertion and 6 h comfort with contact lens wear.

METHODS: Comfort and associated symptoms of dryness were assessed in 15 experienced contact lens wearers. Subjects wore a low Dk lens in one eye and a silicone hydrogel in the other and participated in four separate trials involving no lubricant (baseline), saline, and two commercially available lubricants of differing viscosity. The in-eye lubricants were used immediately following lens insertion and every 2 h postinsertion for a 6 h wear period.

RESULTS: Postlens insertion comfort was significantly better for both lens types when lubricants or saline were used compared with no lubricant use. After 6 h lens wear, comfort was influenced by lens type and not by in-eye lubricant or saline use. Also after 6 h lens wear, less dryness sensation was reported for silicone hydrogel lenses when using lubricants but not saline.

DISCUSSION: Although lubricant use does help reduce dryness symptoms with silicone hydrogel lens wear, there appears to be minimal longer-term benefit to comfort. Furthermore, increased lubricant viscosity did not lead to improved longer-term comfort.

Abstract: Azasite for blepharitis

I was looking forward to seeing something in print on this after all the anecdotal reports from patients and doctors. This looks promising.

For the miracle-seekers ("Where's my magic goop?") amongst us, please note that this study did NOT explore the effects of Azasite on its own. It compared compresses only to compresses plus Azasite and found a significant improvement to results when Azasite was added. I contacted the doctor who did this study and asked him to let me know what kind of compress it was.

Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis.
Adv Ther. 2008 Sep 9. [Epub ahead of print]
Luchs J.

INTRODUCTION: Azithromycin, a broad-spectrum antibiotic with potent anti-inflammatory activities, has the potential to effectively treat blepharitis, an inflammatory disease of the eyelid with abnormal eyelid flora as an etiologic determinant. The present study compared the efficacy of topical azithromycin ophthalmic solution 1% (AzaSite(R); Inspire Pharmaceuticals, Inc, NC, USA) combined with warm compresses (azithromycin group) to warm compresses alone (compress group) in patients with posterior blepharitis.

METHODS: Twenty-one patients diagnosed with posterior blepharitis were randomized in an open-label study to receive either azithromycin plus warm compresses (10 patients), or compresses alone (11 patients). All patients were instructed to apply compresses to each eye for 5-10 minutes twice daily for 14 days. Each eye in the azithromycin group also received azithromycin solution (1 drop) twice daily for the first 2 days followed by once daily for the next 12 days. Patients were evaluated at study initiation (visit 1) and at end of treatment (visit 2) for the severity of five clinical signs: eyelid debris, eyelid redness, eyelid swelling, meibomian gland (MG) plugging, and the quality of MG secretion. At visit 2, patients also rated their degree of overall symptomatic relief.

RESULTS: Twenty patients completed the study. At visit 2, patients in the azithromycin group demonstrated significant improvements in MG plugging, MG secretions, and eyelid redness as compared with the compress group. In the azithromycin group, MG plugging resolved completely in three patients and MG secretion returned to normal in two patients; no such results were seen in the compress group. Furthermore, a higher percentage of patients in the azithromycin group rated overall symptomatic relief as excellent or good. Visual acuity measurements and biomicroscopic evaluation revealed no ocular safety issues.

CONCLUSION: Azithromycin ophthalmic solution in combination with warm compresses provided a significantly greater clinical benefit than warm compresses alone in treating the signs and symptoms of posterior blepharitis.

NIH grant to doctoral student working on dry eye

For those who are wondering where the NIH is, here's one for you... going to lacrimal gland study. It's not a lot of money but every bit counts.

Link to news article

(Media-Newswire.com) - USC School of Pharmacy senior research associate Liana Asatryan and doctoral student Janette Contreras have received an award from the National Institutes of Health to fund their respective projects in drug discovery and development....

Contreras won the Ruth L. Kirschstein Pre-Doctoral Fellowship, an NIH award created to promote diversity in health-related research. Contreras works in the lab of Sarah Hamm-Alvarez, the Gavin S. Herbert Professor in Pharmaceutical Sciences and chair of the Department of Pharmacology and Pharmaceutical Science.

Contreras’ fellowship provides $123,000 over three years, financing her work on the treatment of diseases of the eye. Specifically, Contreras will contribute to the Hamm-Alvarez lab’s focus on dry eye and Sjögren’s disease.

“My work focuses on diseases that target the lacrimal cells in the eye,” Contreras said. “We hope to find efficient ways to deliver medicines into the affected cells. Ultimately, this work may lead to treatments as well as cures for these ailments.”

By studying the role of the viral receptors in the eye’s lacrimal gland and how a virus travels into the gland, Contreras is trying to flip that delivery route and use it as a way for medicines to enter the affected eye molecules.

Abstract: Topical apolipoprotein A-1

Interesting. The results sound good - translate to humans and I'll be happy.

Topical apolipoprotein A-1 may have a beneficial effect on the corneal epithelium in a mouse model of dry eye: a pilot study.
Eye Contact Lens. 2008 Sep;34(5):287-92.
Nyunt AK, Ishida Y, Yu Y, Shimada S.
Menicon Co, Ltd, Global Business division, Japan.

PURPOSE: Dry-eye syndrome affects millions of individuals and it is essential to develop effective therapeutic agents for the treatment of this complex condition. The goal of this study was to evaluate the effect of apolipoprotein A (ApoA)-1 and its synergistic action with d-pantethine (DP) on corneal epithelial disorders in dry-eye mouse model.

METHODS: Aqueous tear production of C57BL/6J Jms Slc male mice aged 10 to 12 weeks were inhibited by subcutaneous scopolamine injection and mice were placed in a continuous airflow blower to create desiccating environmental stress. During desiccation, 1 eye of each mouse was treated with ApoA-1 (0.01%, 0.04%, or 0.1%) or ApoA-1 (0.04%) + DP (0.05%, 0.1%, or 0.2%) and the other control eye was instilled with phosphate-buffered saline 4 times daily for 5 days. Phenol red thread test, corneal fluorescein staining (score, 0-4), and measurement of corneal epithelial thickness measurements were performed.

RESULTS: Significant reductions of staining scores and higher corneal epithelial thickness values were observed in both ApoA-1- and ApoA-1 + DP-treated groups compared with untreated dry-eye mouse and phosphate-buffered saline-treated group.

CONCLUSIONS: These results suggest that ApoA-1 and DP may be potential therapeutic agents for ocular surface epithelial disorders in patients with dry eye.

Abstract: Plugs and contacts

Wow - this is surprising. They put plugs in some contact lens patients and pretended to put plugs in others - and the faked ones were the only ones to show any difference in their tear film.

Eye Contact Lens. 2008 Sep;34(5):261-5.
The impact of punctal occlusion on soft contact lens wearing comfort and the tear film.
Geldis JR, Nichols JJ.
Ohio State University, College of Optometry

OBJECTIVES: The purpose of this report is to describe the impact of punctal occlusion in symptomatic dry eye contact lens wearers and the relation between subjective and objective outcomes.

METHODS: This study was a randomized, controlled, double-masked, single center clinical trial. A previously described dry-eye questionnaire was used to determine subject eligibility. Tear interferometry was performed to evaluate prelens tear film thickness, contact lens center thickness, and postlens tear film thickness. Each subject was randomly assigned to receive the punctal plugs or a sham procedure. At the outcome examination, the subject completed the dry-eye questionnaire and answered one question rating the efficacy of the punctal plug treatment in addition to undergoing tear interferometry using an identical protocol as the first visit.

RESULTS: Nineteen subjects completed both visits of this study. There was a significant improvement in the dry-eye questionnaire scores from baseline to the outcome visit for both the plug (Z = -2.52, P=0.01) and sham groups (Z = -2.93, P=0.003). A significant increase in prelens tear film thickness occurred within the sham group from baseline to the outcome visit (Z = -1.96, P=0.05), but not for the punctal plug group. No other layers measured by interferometry were shown to change significantly for either group.

CONCLUSIONS: Results comparing the sham and plug groups were not significantly different from each other with regards to the questionnaire score and treatment benefit assessment, indicating either the treatment effect was not detected, although present, or punctal occlusion had no treatment effect at all.