Saturday, October 10, 2009

Abstract: Dry eye and quality of life

[Dry eye and quality of life.]
Arch Soc Esp Oftalmol. 2009 Sep;84(9):451-8.Links
[Article in Spanish]

García-Catalán MR, Jerez-Olivera E, Benítez-Del-Castillo-Sánchez JM.
Unidad de Superficie e Inflamación Ocular del Hospital Clínico San Carlos, Madrid, España.

PURPOSE: To evaluate the relation between dry eye severity and quality of life.

METHODS: 40 participants (19 with dry eye and 21 normal controls) underwent slit-lamp examination and Schirmer test to evaluate dry eye severity. Quality of life was evaluated with OSDI (Ocular Surface Disease Index) and VFQ-25 (Visual Function Questionnaire-25).

RESULTS: The OSDI total score was significantly greater in patients suffering dry eye. However, BUT (break-up time) and VFQ-25 total score were significantly lower than in control subjects. In dry eye patients several statistically significant correlations (p<0.05) were found: OSDI with VFQ-25 total score (r=-0.62), BUT with corneal staining (r=-0.50) and Schirmer (0.66), BUT with OSDI total score, OSDI-symptoms and OSDI-triggers (r=-0.56, -0.56, -0.60); corneal staining with OSDI total score and OSDI-symptoms (r=0.55, 0.54), BUT with VFQ-25 total score, VFQ-25 ocular pain, mental function and role function. (r=0.56, 0.51, 0.63, 0.56); corneal staining with VFQ-25 total score, VFQ-25 ocular pain and near vision (r=-0.57, -0.49, -0.62).

CONCLUSION: Quality of life is decreased in patients with dry eye. OSDI and VFQ-25 questionnaires are valid instruments for measuring the impact of dry eye disease. BUT and corneal staining provide an indirect measurement of quality of life (Arch Soc Esp Oftalmol 2009; 84: 451-458).

Abstract: Sjogrens-like patients who don't fit the profile

Increased prevalence of antibodies to thyroid peroxidase in dry eyes and mouth syndrome or sicca asthenia polyalgia syndrome.
J Rheumatol. 2009 Aug;36(8):1626-30. Epub 2009 Jul 15.
Mavragani CP, Skopouli FN, Moutsopoulos HM.
Rheumatology Unit, Athens General Hospital "G. Gennimatas";Department of Nutrition and Dietetics, Harokopio University; and Department of Pathophysiology, School of Medicine, Athens, Greece.

OBJECTIVE: A subset of patients presenting with sicca features suggestive of primary Sjögren's syndrome (pSS) do not fulfill diagnostic or histopathological criteria. This presentation was previously designated as dry eyes and mouth syndrome (DEMS) or sicca asthenia polyalgia syndrome (SAPS). We sought to define the underlying clinical, laboratory, and histological features of these patients.

METHODS: The study population consisted of 27 consecutive patients with DEMS/SAPS; 54 patients with pSS served as controls. Medical charts were retrospectively evaluated for clinical and serological data and frozen sera were tested for the presence of antibodies against HIV, hepatitis C virus, and thyroid antigens. Immunohistochemical analysis of paraffin embedded tissues was also performed.

RESULTS: Sicca symptoms and nonspecific musculoskeletal pain were the commonest clinical features of patients with DEMS/SAPS; positive titers of antibodies against thyroid peroxidase was the main underlying abnormality found in 16 out of 27 (59.2%) of patients with DEMS/SAPS compared to 11 out of 54 (20.4%) of pSS controls (p = 0.0009). Histological analysis of the minor salivary gland (MSG) biopsies of patients with DEMS/SAPS disclosed a mild inflammatory infiltration of the interstitial tissue with a predominantly perivascular distribution.

CONCLUSION: Patients with DEMS/SAPS present with sicca features and nonspecific musculoskeletal complaints, have high prevalence of antithyroid antibodies, and their MSG biopsies demonstrate a mild interstitial lymphocytic infiltration with a predominantly perivascular distribution. In the setting of clinical practice, we propose that in the presence of DEMS/SAPS testing for antithyroid antibody should be performed.

Abstract: Albumin

As mentioned in a previous post this is not currently being studied but hopefully will be in the future.

[Albumin eye drops for treatment of ocular surface diseases.]
Ophthalmologe. 2009 Oct 8. [Epub ahead of print]
[Article in German]
Unterlauft JD, Kohlhaas M, Hofbauer I, Kasper K, Geerling G.
Klinik für Augenheilkunde, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Deutschland.

For more than 10 years eye drops made from autologous serum have become an established therapy to support corneal wound healing in ocular surface diseases, such as persistent epithelial defects and dry eye. Serum eye drops can only be dispensed by institutions which have obtained a specific license from the appropriate local authorities and this applies to only a few institutes in Germany. The main protein component of serum is albumin which is commercially available as a quality controlled medical product from the pharmaceutical industry and could thus be used as an alternative to autologous serum eye drops. The wound healing effect of albumin eye drops has already been demonstrated in vitro. Here we outline the therapeutic principles and present our first clinical experiences with eye drops made from albumin in the treatment of ocular surface disorders.

Friday, October 9, 2009

And on the home front...

Every so often I get the urge to write about something other than dry eye... and this is one of those days.

On the farm, the garden is winding down though we're still getting tomatoes, squash and (finally) eggplants. Also getting lots of peppers from the greenhouse. The apple trees are still showering us with far more fruit than I can deal with and they are sooo tasty.

The hens are being naughty. Very, very naughty. They have taken to hiding their eggs - always a risk with free-ranging chickens - and so we're only getting about half as many as we should be. It's all one hen's fault. She gets in one of the nest boxes and sits there half the day and kicks up a fuss at anybody that comes near her. At first, all the hens would line up nicely and wait their turn but they eventually got tired of waiting for Ms. Broody and started finding better spots. So, today I finally gritted my teeth and shut them in the chicken tractor for the day. If they get tired of waiting, they can lay in a corner of the roost which has plenty of straw.

We now have two more batches of birds, all for meat. Actually, two plus. There are three birds that were hatched from our own Australorp eggs and they should be ready to go in another couple of weeks. Then there's a mixed batch (variety of breeds), originally 25 but now down to 17 after a predator attack, that should be ready for the knife in about 6 weeks or so, and finally my husband talked me into getting yet another batch of 25 which just arrived yesterday and is peeping up a storm in their brooder in the mud room. Those ones are Barred Rocks, bought for no better reason than that the Mixed Bird Surprise batch that I got the last time had several of them and I thought they were pretty. As 2-day-olds they are adorable.

By the way, if you've never had home-raised organic chicken, you are missing out.

We've had a beautiful fall, warm and sunny a lot of the time though we're getting into the 30s here at night now, and I have been absolutely itching to get outside and dig up the garden or do SOMETHING, but just have not had any spare time. Hopefully I will still get a chance before the weather turns to the dreaded Grey, Cold and Wet of Puget Sound Novembers.

Our new (well, new to us) furnace is now finally fully installed and keeping things toasty warm. I think next I'll be firing up the humidifier.

As to family... Many months ago I posted (probably on the bulletin board, not here, come to think of it) about my husband having a degenerative brain disorder. Things have changed, so I thought I'd give a little update. Panos had severe dementia symptoms last year and because of his history, we had tentatively concluded it was primary. However, with a change of medications and a change of scene (his mother gave me a caregiving break for quite awhile earlier this year) that has actually backed off and the neurologist has now concluded it was pseudodementia, which is a huge relief. And as an aside... if you think dry eye is a complex area of medicine or if you've ever felt there's some kind of training gap between ophthalmology and dermatology... the spectrum from neurology to psychiatry is worse, trust me. Google frontotemporal dementia for more info.

So meantime, while I'm terribly thankful that we no longer seem to have a life-limiting diagnosis there is plenty on the plate with a cocktail of psychiatric and cognitive disorders of unknown origin. Between caregiving, running a little business and homeschooling my little girl I am in no danger of boredom anytime soon. :-)

Tuesday, October 6, 2009

Abstract: Flaps & dry eye

Nothing particularly new here and I sure wish they'd make studies like this more useful by evaluating a longer interval than one month postop. Also would be helpful to know how they evaluated symptoms (why is it that the refractive surgery studies seem to be among the least likely to specify this in the methods in the abstract?). But I did think it was interesting that while intralase flaps seemed to create quite a bit less dry eye, amongst the keratome folks the thickness of the flap did not appear to matter (except, of course, for all the reasons other than dry eye why flap thickness matters).

Dry eye associated with laser in situ keratomileusis: Mechanical microkeratome versus femtosecond laser.
J Cataract Refract Surg. 2009 Oct;35(10):1756-60.
Salomão MQ, Ambrósio R Jr, Wilson SE.
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
PURPOSE: To compare the incidence of laser in situ keratomileusis (LASIK)-associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser and a mechanical microkeratome.

SETTING: Cole Eye Institute, Cleveland, Ohio, USA.

METHODS: Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry-eye treatment were evaluated preoperatively and 1 month postoperatively.

RESULTS: The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 mum +/- 14 [SD]) and the microkeratome group (131 +/- 25 mum) was statistically significant (P<.001). The incidence of LASIK-associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK-induced dry eye.

CONCLUSIONS: Eyes with femtosecond flaps had a lower incidence of LASIK-associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK-induced dry eye.

Abstract: New treatment for corneal neovascularization?

Mouse-stage and tested under pretty extreme conditions but interesting results and some of you with persistent issues of this type might want to be following developments on this one.

Inhibitory effects of polysaccharide extract from Spirulina platensis on corneal neovascularization.
Mol Vis. 2009 Sep 24;15:1951-61.
Yang L, Wang Y, Zhou Q, Chen P, Wang Y, Wang Y, Liu T, Xie L.
State Key Laboratory Cultivation Base, Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China.

PURPOSE: To assess the effects of polysaccharide extract from Spirulina platensis (PSP) on corneal neovascularization (CNV) in vivo and in vitro.

METHODS: PSP was extracted from dry powder of Spirulina platensis. Its anti-angiogenic activity was evaluated in the mouse corneal alkali burn model after topical administration of PSP four times daily for up to seven days. Corneal samples were processed for histochemical, immunohistochemical, and gene expression analyses. The effects of PSP on proliferation, migration, tube formation, and serine threonine kinase (AKT) and extracellular regulated kinase1/2 (ERK1/2) signaling levels in vascular endothelial cells were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) and carboxyfluorescein succinimidyl ester (CFSE) labeling assays, wound healing assay, Matrigel tube formation assay, and western blot.

RESULTS: Topical application of PSP significantly inhibited CNV caused by alkali burn. Corneas treated with PSP showed reduced levels of platelet endothelial cell adhesion molecule (CD31) and stromal cell-derived factor 1 (SDF1) proteins, reduced levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), SDF1, and tumor necrosis factor-alpha (TNF-alpha) mRNAs, and an increased level of pigment epithelium-derived factor (PEDF) mRNA. These are parameters that have all been related to CNV and/or inflammation. In human vascular endothelial cells, PSP significantly inhibited proliferation, migration, and tube formation in a dose-dependent manner. Furthermore, PSP also decreased the levels of activated AKT and ERK 1/2.

CONCLUSIONS: These data suggest that polysaccharide extract from Spirulina platensis is a potent inhibitor of CNV and that it may be of benefit in the therapy of corneal diseases involving neovascularization and inflammation.

Drug news: Macusight's Perceiva (Sirolimus)

New to me. This drug is in four different Phase II studies looking at it for use in three different conditions, one of which is dry eye.

Here's a link to the clinical trial information (this is completely enrolled but in case you want to read about it)

And here's a news article from Sept 30th:

MacuSight(R) Provides Clinical Development Update for Perceiva(TM)

UNION CITY, Calif., Sept. 30 /PRNewswire/ -- MacuSight, a developer of innovative therapeutics for the treatment of severe ocular diseases and conditions, today provided a clinical development update for Perceiva, the company's proprietary ocular sirolimus product. The company has completed patient enrollment in four ongoing Phase 2 clinical trials of Perceiva and plans to announce data from these studies in the first half of 2010. All four studies are being conducted at investigational sites in the United States. These studies, which are evaluating Perceiva as a treatment for diabetic macular edema (DME), neovascular (wet) age-related macular degeneration (wet AMD) and dry eye syndrome, are part of MacuSight's broad Phase 2 Perceiva clinical program which spans five major ocular disease indications....

MacuSight's fourth Phase 2 trial, in which the company is using Perceiva to evaluate the potential role for sirolimus in the treatment of dry eye syndrome, has successfully enrolled 143 patients at four investigational sites. For this trial, MacuSight worked with Ora, Inc., a leading global clinical research organization located in Andover, MA. As part of this randomized, dose-ranging, placebo-controlled study, patients receive a single subconjunctival injection of Perceiva at baseline. Investigators will evaluate signs and symptoms of dry eye over a period of 28 days following a single injection.

Abstract: Corneal nerve regeneration



LASIK dry eye patients, don't get too excited yet, it's only at the bunny-trial stage but I'll definitely be following this one closely as it appears very promising. And looky, we are even mentioned in the conclusions.

Emphases mine.

PEDF plus DHA Induces Neuroprotectin D1 Synthesis and Corneal Nerve Regeneration after Experimental Surgery.
Invest Ophthalmol Vis Sci. 2009 Sep 24. [Epub ahead of print]
Cortina M, He J, Li N, Bazan N, Bazan H.
Ophthalmology, LSU, Chicago, United States.

Purpose: Define whether pigment epithelial-derive growth factor (PEDF) together with docosahexaenoic acid (DHA) enhances synthesis of neuroprotectin D1 (NPD1) and regeneration of corneal nerves damaged post-surgery.

Methods: A corneal stromal dissection was performed in the left eye of adult New Zealand rabbits treated with DHA+PEDF, PEDF, or DHA for 6 weeks. In vivo confocal images of the corneas were obtained at 2, 4 and 8 weeks and nerve areas quantified. At 8 weeks post-treatment, corneas were stained with tubulin betaIII antibody, and epithelial nerve area, sub-basal and stromal nerve plexus were quantified. At 1 and 2 weeks post-treatment, lipids were extracted from corneas and synthesis of NPD1 was analyzed by mass spectrometry. Epithelial cell density was quantified by confocal microscopy 8 weeks post-surgery.

Results: In vivo confocal images at 2 and 4 weeks post-surgery showed a 2.5-fold increase in corneal nerve area in PEDF+DHA-treated animals, compared with control animals. Increased nerve surface area in epithelia, sub-epithelial and stroma was observed in rabbits treated for 8 weeks with PEDF+DHA. PEDF or DHA alone did not produce a significant increase. NPD1 synthesis peaked at 1 week and was four times higher in PEDF+DHA-treated group, compared with controls.

Conclusions: PEDF+DHA promotes regeneration of corneal nerves. Neurotrophin-mediated NPD1 synthesis is suggested to precede nerve regeneration by demonstration of its accumulation upon addition of DHA and PEDF at earlier time points. Therefore, this signaling mechanism upregulates cornea nerve regeneration and may be targeted in neurotrophic keratitis, dry eye after refractive surgery, and other corneal diseases.

Abstract: Bleph & doxy

A common question for those trying Rx drug is, how long do I keep using it before I should expect to see improvement (if it IS going to help)? This one may answer that as regards doxycycline use for some patients.

In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis.
Eur J Ophthalmol. 2009 Sep-Oct;19(5):708-16.
Iovieno A, Lambiase A, Micera A, Stampachiacchiere B, Sgrulletta R, Bonini S.
Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Ophthalmology, University of Roma Campus Bio-Medico, Roma - Italy.

PURPOSE: Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis.

METHODS: Eight patients (6 male, 2 female; mean age 45.7+/-17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0-3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity.

RESULTS: An improvement in TSS (4.5+/-1.1 vs 2.7+/-1.5) and TSyS (6.6+/-1.3 vs. 3.1+/-1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed.

CONCLUSIONS: This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation.

Abstract: Resistance to antibiotics.

Interesting one here about increase in resistance to antibiotics, implications in ocular infection (including blepharitis) and what can/should be done about it.

Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics.

Clin Ophthalmol. 2009;3:507-21. Epub 2009 Sep 24.
Bertino JS.
College of Physicians and Surgeons, Columbia University, New York, NY, USA;
PURPOSE: This article reviews the effects of the increase in bacterial resistance on the treatment of ocular infections.

DESIGN: Interpretive assessment.

METHODS: Literature review and interpretation.

RESULTS: Ocular bacterial infections include conjunctivitis, keratitis, endophthalmitis, blepharitis, orbital cellulitis, and dacryocystitis. Treatment for most ocular bacterial infections is primarily empiric with broad-spectrum antibiotics, which are effective against the most common bacteria associated with these ocular infections. However, the widespread use of broad-spectrum systemic antibiotics has resulted in a global increase in resistance among both Gram-positive and Gram-negative bacteria to a number of the older antibiotics as well as some of the newer fluoroquinolones used to treat ophthalmic infections. Strategies for the prevention of the increase in ocular pathogen resistance should be developed and implemented. In addition, new antimicrobial agents with optimized pharmacokinetic and pharmacodynamic properties that have low toxicity, high efficacy, and reduced potential for the development of resistance are needed.

CONCLUSIONS: New antimicrobial agents that treat ocular infections effectively and have a low potential for the development of resistance could be a part of strategies to prevent the global increase in ocular pathogen resistance.

Abstract: Antiinflammatory therapy for dry eye

Nothing new here - brief summary of a literature review. Emphasis (below) mine.

Advancements in anti-inflammatory therapy for dry eye syndrome.
Optometry. 2009 Oct;80(10):555-66.
McCabe E, Narayanan S.
Pennsylvania College of Optometry at Salus University, Elkins Park, Pennsylvania.

PURPOSE: The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting.

METHODS: The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome.

RESULTS: Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects.

CONCLUSIONS: Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.