Monday, July 20, 2009

Support groups: Stuart, FL

East Florida Eye Institute in Stuart, FL is resuming monthly dry eye support group meetings. They will have one in August and I will post again when they have fixed a date.

Abstract: Mice blah blah blah improvement blah blah decreased inflammation

Confession: I start flagging even at T cell talk these days. When we get to CCR2 antagonists, interleukins 1alpha and 1beta my attention's gone until the conclusions, which have some of the right words.

Arch Ophthalmol. 2009 Jul;127(7):882-7. Amelioration of murine dry eye disease by topical antagonist to chemokine receptor 2.

Goyal S, Chauhan SK, Zhang Q, Dana R.
Schepens Eye Research Institute, Boston, MA 02114, USA.

OBJECTIVE: To determine the effect of a topical antagonist to the chemokine receptor 2 (CCR2) in a murine model of dry eye disease.

METHODS: The effects of a topical CCR2 antagonist and a vehicle control treatment were studied in murine dry eyes. A controlled environment chamber induced dry eye by exposing mice to high-flow desiccated air. Corneal fluorescein staining and enumeration of corneal CD11b(+) and conjunctival CD3(+) T cells were performed in the different groups. Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the cornea and conjunctiva.

RESULTS: Eyes receiving the formulation containing CCR2 antagonist showed a significant decrease in corneal fluorescein staining and decreased infiltration of corneal CD11b(+) cells and conjunctival T cells compared with the vehicle-treated and untreated dry eye groups. The CCR2 antagonist also significantly decreased messenger RNA expression levels of interleukins 1alpha and 1beta in the cornea, and tumor necrosis factor alpha and interleukin 1beta in the conjunctiva.

CONCLUSION: Topical application of CCR2 antagonist is associated with significant improvement in dry eye disease and is reflected by a decrease in inflammation at the clinical, molecular, and cellular levels. Clinical Relevance Topical application of CCR2 antagonist may hold promise as a therapeutic modality in dry eye disease.

Abstract: Dry eye in Canada

Hmmmm. I am sure some of my Canadian readers are hoping their doctor was privy to this 'consensus'!

If not, and your doctor is still offering you a generic "dry eye" diagnosis, tears and plugs and goodbye, my suggestion is to print out this statement below and fax it to your doctor the day before your next appointment, along with a brief bullet point synopsis of your goals for the appointment.

Management of dysfunctional tear syndrome: a Canadian consensus.
Can J Ophthalmol. 2009 Aug;44(4):385-94.
Jackson WB.
University of Ottawa Eye Institute, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario, Canada.

Dry eye complaints are common, have a diverse etiology, and result from disruption of the normal tear film; hence, the term "dysfunctional tear syndrome." Recent research has shown that ocular surface disorders have an inflammatory origin, that inflammation of the ocular surface does not always manifest as "red eye," and that a patient does not have to have a systemic autoimmune disease to experience a local, ocular autoimmune event. A panel of Canadian cornea and external disease subspecialists met and developed a questionnaire and treatment algorithm to aid the comprehensive ophthalmologist. Management of ocular surface disorders begins with a review of the patient's medical history, with particular attention to medication use, and a thorough ophthalmological examination. Use of a simple questionnaire can aid in the diagnosis. A variety of treatment modalities are available, the most effective of which are those that target the underlying inflammatory process with the goal of restoring the normal tear film. A treatment algorithm is presented that matches the severity of symptoms with the intensity of treatment. Lifestyle modifications, regular hygiene, and tear supplements may be sufficient in patients with mild symptoms. Anti-inflammatory medications (topical cyclosporin A, short courses of topical steroids, and [or] oral tetracyclines) and physical measures (punctal plugs, moisture-retaining eye wear) are implemented for those with moderate-to-severe symptoms. Autologous serum tears, scleral contact lenses, and surgery are reserved for patients with severe symptoms who have an unsatisfactory response to anti-inflammatory medications. Patients with lid disease or rosacea and those with allergic conditions should be identified during the initial encounter and should receive specific therapy to relieve their symptoms.

Abstract: OMGD treatments & evaluation with confocal

This is kind of an interesting one, studying obstructive meibomian gland disease via confocal microscopy in patients treated with an antiinflammatory or just with unpreserved tears and sodium hyaluronate. Unsurprisingly, the artificial tears really didn't improve anything clinically. Wish there had been some comparison with other treatments.

Graefes Arch Clin Exp Ophthalmol. 2009 Jun;247(6):821-9. Epub 2008 Dec 20.
The evaluation of the treatment response in obstructive meibomian gland disease by in vivo laser confocal microscopy.

Matsumoto Y, Shigeno Y, Sato EA, Ibrahim OM, Saiki M, Negishi K, Ogawa Y, Dogru M, Tsubota K.
Johnson & Johnson Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo, Japan.

PURPOSE: To evaluate the status of periglandular inflammation, ocular surface and tear function alterations in patients with obstructive meibomian gland disease (OMGD) by in vivo confocal microscopy before and after anti-inflammatory treatment, and to compare the results with patients receiving only topical non-preserved artificial tears and sodium hyaluronate eye drops without anti-inflammatory agents.

METHODS: Thirty-two eyes of 16 OMGD patients receiving anti-inflammatory treatment (treatment group) and 22 eyes of 11 OMGD patients receiving only topical non-preserved artificial tears and sodium hyaluronate eye drops (control group) were recruited in this prospective study. All subjects underwent slit-lamp examinations, tear film break-up time (BUT) measurements, fluorescein and Rose-Bengal stainings, Schirmer test capital I, Ukrainian without anesthesia, transillumination of the lids (meibography), and in vivo laser confocal microscopy of the lids (HRTII-RCM).

RESULTS: The mean BUT, fluorescein staining scores, and inflammatory cell densities observed by in vivo confocal microscopy improved significantly in the group receiving anti-inflammatory treatment (p < 0.05), whereas no significant alterations of these parameters were observed in the group not receiving anti-inflammatory agents (p > 0.05).

CONCLUSIONS: In vivo confocal microscopy was able to effectively demonstrate the treatment responses in patients with OMGD. Inflammatory cell density calculation seems to be a promising new parameter of in vivo confocal microscopy in the evaluation of treatment responses.

Abstract: MMP9 as a dry eye marker

Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome.
Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3203-9. Epub 2009 Feb 28.
Chotikavanich S, de Paiva CS, Li de Q, Chen JJ, Bian F, Farley WJ, Pflugfelder SC.
Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

PURPOSE: To evaluate production and activity of metalloproteinase (MMP)-9 on the ocular surface of patients with dysfunctional tear syndrome (DTS) and determine any correlation between MMP-9 activity and clinical parameters.

METHODS: Forty-six patients with newly diagnosed DTS and 18 control subjects were recruited. Complete ocular surface examinations were performed. Tear MMP-9 activity was assessed with an MMP-9 activity assay in 1 microL of unstimulated tear fluid. Using conjunctival epithelial cells from 19 patients with DTS and 16 controls, levels of MMP-9 and its regulating cytokine mRNA transcripts were evaluated by semiquantitative real-time PCR.

RESULTS: Each of four DTS severity-based groups had significantly higher mean MMP-9 activities than did the control group, which was 8.39 +/- 4.70 ng/mL. The DTS4 group had the highest MMP-9 activity (381.24 +/- 142.83 ng/mL), for which the mean was significantly higher than that of other DTS groups. In addition, patients with DTS had significantly higher levels of IL-1beta, IL-6, TNF-alpha, and TGF-beta1 mRNA transcripts in their conjunctival epithelia than did the control subjects. Tear MMP-9 activities showed significant correlation with symptom severity scores, decreased low-contrast visual acuity, fluorescein tear break-up time, corneal and conjunctival fluorescein staining, topographic surface regularity index (SRI), and percentage area of abnormal superficial corneal epithelia by confocal microscopy.

CONCLUSIONS: Tear MMP-9 activity was significantly higher in patients with DTS. This activity was associated with increased mRNA expression of MMP-9 and its regulating genes and correlated strongly with clinical parameters. MMP-9 appears to be a potentially useful biomarker for diagnosing, classifying, and monitoring DTS.