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

Zowie.

Seriously.

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.

Abstract: Systane, Optive, and visual acuity

For your reading ease...

PEG/PG = Systane

CMC/glycerin = Optive

(at least I'm assuming so as those are the only products I know with the indicated active ingredients)


The effects of lubricant eye drops on visual function as measured by the Inter-blink interval Visual Acuity Decay test.
Clin Ophthalmol. 2009;3:501-6. Epub 2009 Sep 24.
Torkildsen G.
Andover Eye Associates, Andover, MA, USA.

OBJECTIVE: The purpose of the current study was to evaluate the effects of two marketed ocular lubricants on the visual decay in dry eye patients using the Inter-blink interval Visual Acuity Decay (IVAD) test.

METHODS: This controlled, randomized, double-masked crossover study compared the effects of a polyethylene glycol/propylene glycol-based (PEG/PG) tear and a carboxymethylcellulose sodium (CMC)/glycerin tear on the visual acuity decay between blinks of dry eye patients. At visit 1 (Day 0), baseline IVAD measurements were recorded prior to instillation of a single drop of randomized study medication. IVAD testing was repeated at 15-, 45-, and 90-minutes post-instillation. Reading rate and functional blink rate were also evaluated. At the second visit (Day 7 +/- 3), study procedures were repeated using crossover treatment.

RESULTS: Forty-eight (48) subjects with dry eye (61.1 +/- 14.8 years old, 79.2% female, 95.8% white) completed the study. Treatment with the PEG/PG-based tear demonstrated statistically significantly longer time to one-line loss of best-corrected visual acuity (BCVA) as determined by the IVAD test at 90 minutes post-instillation compared to the CMC/glycerin tear (P = 0.0365). Measurements of median time at BCVA, reading rate, and functional blink rate were similar for both treatments. Both formulations were well tolerated in the population studied.

CONCLUSIONS: Treatment with the PEG/PG-based tear demonstrated statistically significant improved maintenance of visual acuity between blinks at 90 minutes post-instillation compared to the CMC/glycerin tear. This is the first study to demonstrate the ability of an artificial tear to extend visual acuity maintenance between blinks, as measured by the IVAD test.