Thursday, December 20, 2007

Study: Mizoribine in Sjogrens treatment

Just a passing mention and no details as to methodology or degree of improvement in the abstract, but since this does mention dry eye improvement, Sjogrens patients may want to check it out.

Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial.

Nakayamada S, Saito K, Umehara H, Ogawa N, Sumida T, Ito S, Minota S, Nara H, Kondo H, Okada J, Mimori T, Yoshifuji H, Sano H, Hashimoto N, Sugai S, Tanaka Y.
Mod Rheumatol. 2007;17(6):464-9. Epub 2007 Dec 20

This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150;Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients' own assessments of dry mouth and dry eyes, the investigators' assessment of oral sicca symptoms, and the investigators' overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.

Study: More on the eyelid wipers

I don't have any particular comments, but I've always been interested in following what they're writing & studying about lid movement because of implications for dry eye.

Elastohydrodynamics of the Eyelid Wiper.
Jones MB, Fulford GR, Please CP, McElwain DL, Collins MJ.
Bull Math Biol. 2007 Dec 8

This paper presents an elastohydrodynamic model of the human eyelid wiper. Standard lubrication theory is applied to the fluid layer between the eyelid wiper and ocular surface. The role of the lubrication film is to reduce the shear stresses by preventing solid to solid contact between the eyelid wiper and ocular surface. For the lubrication film to be effective, it is required that the orientation of the eyelid wiper changes between the opening and closing phases of a blink. In order to model this, the hydrodynamic model is coupled with an elastic mattress model for the soft tissue of the eyelid wiper and ocular surface. This leads to a one-dimensional non-linear partial differential equation governing the fluid pressure in the lubrication film. In order to solve the differential equation, a loading condition or constraint equation must be specified. The resulting system is then solved numerically. The model allows predictions of the tear film flux from under the upper eyelid, as well as normal and shear stresses acting on the ocular surface. These factors are important in relation to dry eye syndrome, deformation of the cornea and contact lens design. It is found that the pressure and shear stress under the eyelid act across a length of approximately 0.1 mm which is consistent with clinical observations. It order to achieve a flow of tears from under the upper eyelid during a blink, the model requires that the normal force the eyelid applies to the ocular surface during the closing phase of the blink is significantly higher than during the opening phase of the blink.

Study: Botox blah blah dry eye blah blah mice

Sigh, these molecular-level things... I need a translator. The only thing that kind of jumped off the page at me from this one was that some of the inflammatory stuff was equally impervious to cyclosporine, corticosteroids and artificial tears.

Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model.
Park CY, Zhuang W, Lekhanont K, Zhang C, Cano M, Lee WS, Gehlbach PL, Chuck RS.
Mol Vis. 2007 Nov 29;13:2222-32.

PURPOSE: To determine the effect of keratoconjunctivitis sicca, induced by botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the lacrimal gland (LG). And to determine the effect of various topical anti-inflammatory agents on the resulting cytokine levels.

METHODS: Forty-two mice (eight-week-old, female, CBA/J) were divided into six groups. Four groups were injected with BTX-B into both lacrimal glands, one group was injected with saline into both LG (Sal, n=7), and one group served as an uninjected control (Con, n=7). The four groups of BTX-B injected mice were then assigned to a treatment group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3. Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in each group). Corneal fluorescein staining was evaluated one, two, and four weeks after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX) and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis for inflammatory cytokines and their receptors, real time reverse-transcriptase polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti-mouse CD3e monoclonal antibody were then performed on LG tissue.

RESULTS: BTX-B injection into the LG effectively induced dry eye in mice two and four weeks following injection. Microarray data identified the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, IL-12, and macrophage migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and toll-interacting protein (Tollip) as candidates for validation by real time RT-PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and 4 regardless of treatment. Tollip and IL-1 expressions were increased in some groups after BTX-B injection regardless of the treatment type. Other cytokines showed no significant changes. LG structures were well maintained without significant T lymphocyte infiltration in all groups.

CONCLUSIONS: Ocular surface change induced by BTX-B injection resulted in an altered expression of various inflammatory cytokines in our murine dry eye model. Alteration of the pathology-induced cytokine profile by topical therapy is reported.

Newsblurb: The office environment & dry eye

Five reasons your office is bad for you

1. Sights for Sore Eyes. According to a study reported in the Survey of Ophthalmology, computer users risk tired, red eyes, burning and blurred or double vision. People blink up to 60 percent less often while looking at the screen, causing dry-eye symptoms. The cornea is also sensitive to office hazards like dry air, airborne paper dust and ventilation fans. To protect yourself, look away from the screen and at a distant object at least every 30 minutes. Use eye drops if you feel strain. And if you wear reading glasses and work at a computer more than an hour a day, researchers recommend a pair of glasses especially designed for the distance you normally sit from the screen.

Newsblurb: Lissamine green

Alright, I've been seeing this creep into the news here and there for the last several weeks so I figured I'd better eventually post about it.

Detecting Dry Eye

...DETECTION: Lissamine green is an eye-drop stain used by ophthalmologists to detect damaged cells on the eye's surface. They turn green under special lighting, helping doctors identify potentially dangerous conditions. Researchers from UT Southwestern Medical Center in Dallas, Texas were able to identify three basic patterns produced by the stain that indicate progressively dangerous conditions. The least severe pattern, known as nasal staining, is indicated by stains limited to the whites of the eyes between the lids toward the nose. The second level appears as stains in the white of the eye between the lids, but toward the ear. This pattern is diagnostic of tear deficiency. The third and most severe level occurs when the stain appears on the cornea.

New drug news: NOVA22007

Per a news item from Novagali Pharma on Tuesday, this is expected to enter Phase III clinical trials in the US in the second quarter of 2008.

In our clinical trial roster on The Dry Eye Zone I previously had this down as already being in Phase III (based on an April press release) but I've relegated it to Phase II till the Phase IIIs actually start.