Monday, August 15, 2011

Abstract: Omega 3/Omega 6 dry eye study

Hm. These results are really quite disappointing all things considered. No, it doesn't mean stop taking your fish oil - as long as you've got a good one, it's good for you even if it isn't helping your eyes :-)

A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients.

To determine whether oral supplementation with omega-3 and omega-6 fatty acids can reduce conjunctival epithelium expression of the inflammatory marker human leucocyte antigen-DR (HLA-DR) in patients with dry eye syndrome (DES).

This 3-month, double-masked, parallel-group, controlled study was conducted in nine centres, in France and Italy. Eligible adult patients with mild to moderate DES were randomized to receive a placebo containing medium-chain triglycerides or treatment supplement containing omega-3 and omega-6 fatty acids, vitamins and zinc. Treatment regimen was three capsules daily. Impression cytology (IC) was performed at baseline and at month 3 to assess the percentage of cells expressing HLA-DR and to evaluate fluorescence intensity, an alternate measure of HLA-DR. Dry eye symptoms and objective signs were also evaluated. Analyses were performed on the full analysis set (FAS) and per-protocol set (PPS).

In total, 138 patients were randomized; 121 patients with available IC were included in the FAS, and of these, 106 patients had no major protocol deviations (PPS). In the PPS, there was a significant reduction in the percentage of HLA-DR-positive cells in the fatty acids group (p = 0.021). Expression of HLA-DR as measured by fluorescence intensity quantification was also significantly reduced in the fatty acids group [FAS (p = 0.041); PPS (p = 0.017)]. No significant difference was found for the signs and symptoms, but there was a tendency for improvement in patients receiving the fatty acids treatment.

Conclusion:  This study demonstrates that supplementation with omega-3 and omega-6 fatty acids can reduce expression of HLA-DR conjunctival inflammatory marker and may help improve DES symptoms.

Acta Ophthalmol. 2011 Aug 11. doi: 10.1111/j.1755-3768.2011.02196.x. [Epub ahead of print]
Brignole-Baudouin F, Baudouin C, Aragona P, Rolando M, Labetoulle M, Pisella PJ, Barabino S, Siou-Mermet R, Creuzot-Garcher C.
Department of Toxicology, Faculty of Biological and Pharmacological Sciences, Paris Descartes University, Paris, France INSERM, U968, Paris, France UPMC Univeristy Paris 06, UMR S 968, Institute of Vision, Paris, France CNRS, UMR 7210, Paris, France Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, France Department of Ophthalmology, University of Messina, Messina, Italy Clinica Oculista, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy CHU Bicêtre Department of Ophthalmology, Assistance Publique, South Paris University, Kremlin-Bicêtre, Paris, France Department of Ophthalmology, University François Rabelais, Bretonneau Hospital, Tours, France Bausch & Lomb, Montpellier, France Department of Ophthalmology, University Hospital, Dijon, France.

Abstract: The latest on sea buckthorn oil

It's always tempting to think... ain't got enough oil? No prob, let's add some systemically or topically. Only, it is never quite that simple.

Remember last year's study of sea buckthorn oil and dry eye? This new study takes it in another direction, indicating that whatever good SBO is doing, it's not acting directly on the lipids but possibly on inflammation or through another mechanism.

Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye.

: Evaporative dry eye is associated with meibomian gland dysfunction and abnormalities of the tear film lipids. Dry eye is known to be affected positively by intake of linoleic and γ-linolenic acids and n-3 fatty acids. Oral sea buckthorn (Hippophaë rhamnoides) (SB) oil, which contains linoleic and α-linolenic acids and antioxidants, has shown beneficial effects on dry eye. The objective was to investigate whether supplementation with SB oil affects the composition of the tear film fatty acids in individuals reporting dry eye.

: One hundred participants were randomized to this parallel, double-blind, placebo-controlled study, which 86 of them completed. The participants daily consumed 2 g of SB or placebo oil for 3 months. Tear film samples were collected at the beginning, during, and at the end of the intervention and 1 to 2 months later. Tear film fatty acids were analyzed as methyl esters by gas chromatography.

: There were no group differences in the changes in fatty acid proportions during the intervention (branched-chain fatty acids: P = 0.49, saturated fatty acids: P = 0.59, monounsaturated fatty acids: P = 0.53, and polyunsaturated fatty acids: P = 0.16).

: The results indicate that the positive effects of SB oil on dry eye are not mediated through direct effects on the tear film fatty acids. Carotenoids and tocopherols in the oil or eicosanoids produced from the fatty acids of the oil may have a positive effect on inflammation and differentiation of the meibomian gland cells.

Cornea. 2011 Sep;30(9):1013-9.
Järvinen RL, Larmo PS, Setälä NL, Yang B, Engblom JR, Viitanen MH, Kallio HP.
From the Department of *Biochemistry and Food Chemistry and †Department of Ophthalmology, University of Turku, Turku, Finland; ‡Turku School of Economics, University of Turku, Turku, Finland; §Turku City Hospital, Turku, Finland; and ¶Karolinska Institutet, Stockholm, Sweden.

Abstract: Optimizing lissamine green staining evaluation

Optimizing evaluation of Lissamine Green parameters for ocular surface staining.

The recently published seminal dry eye workshop proceedings defined Lissamine Green (LG), an organic dye, as a gold standard for demonstrating ocular surface staining. The purpose of the current study was to determine the optimal parameters of 1% LG instillation for the ocular surface examination in dry eye patients.

Prospective and observational quality improvement study.

A quality improvement study evaluated 16 eyes from eight dry eye patients with different levels of severity. LG (1%), in three volumes (5, 10, and 20 μl) was instilled into the conjunctival cul-de-sac, and four masked observers with different levels of clinical expertise examined the patients with and without red filter. The staining pattern of the conjunctiva and cornea was documented with the Oxford scale within 4 min of LG instillation. Optimal volume and inter-observer reliability were assessed.

All dye volumes were tolerated well by all patients. Experienced observers preferred 10 μl volume because of the ease of examination and accuracy. Although instillation of 20 μl yielded similar scores as 10 μl, it resulted in overflow of the lid and facial skin staining. The use of red filter significantly improved reading scores (P<0.01). Inter-observer reliability was higher for conjunctival scores than for corneal scores for all patients. The highest reliability was demonstrated with 10 μl volume and increased with greater experience of the observer.

Ocular surface examination with instillation of 10 μl 1% LG has good inter-observer reliability and is well tolerated. Observation through a red filter facilitates the examination

Eye (Lond). 2011 Aug 12. doi: 10.1038/eye.2011.184. [Epub ahead of print]
Hamrah P, Alipour F, Jiang S, Sohn JH, Foulks GN.
1] Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA [2] Cornea and Refractive Surgery Service, Massachusetts Ear and Eye Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Abstract: Alterations of tear neuromediators in dry eye disease.

Alterations of tear neuromediators in dry eye disease.

To evaluate tear levels of neuromediators in patients with dry eye disease and to identify statistical correlations with the clinical findings.

Nineteen patients with dry eye disease (Sjögren syndrome, n = 5 patients; non-Sjögren syndrome, n = 10; and ocular cicatricial pemphigoid, n = 4) and 12 healthy volunteers were enrolled. The eyes of all participants were evaluated by slitlamp examination, Schirmer testing, fluorescein staining, and tear film break-up time. Grading of dry eye severity was recorded. Tear samples were collected, and substance P, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nerve growth factor (NGF) concentrations were evaluated by enzyme-linked immunoassay and correlated with the clinical findings.

Nerve growth factor tear levels were significantly increased in participants with dry eye disease; CGRP and NPY concentrations were significantly decreased when compared with those in healthy participants. Dry eye severity showed a direct correlation with NGF and an inverse correlation with CGRP and NPY tear levels. Nerve growth factor tear levels showed a direct correlation with conjunctival hyperemia and fluorescein staining results, CGRP directly correlated with Schirmer test values, and NPY inversely correlated with tear film break-up time. Subgroup analysis showed that CGRP and NPY but not NGF were changed in autoimmune (ie, Sjögren syndrome and ocular cicatricial pemphigoid) dry eye disease.

The decreased tear levels of NPY and CGRP in dry eye disease are related to impaired lacrimal function, and tear levels of NGF are more closely related to corneal epithelial damage. Our findings suggest that NPY, CGRP, and NGF could become useful markers of dry eye severity.

Arch Ophthalmol. 2011 Aug;129(8):981-6.
Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S.
Department of Ophthalmology, University of Rome, Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Rome, Italy.

Abstract: Lit review of ocular surface harm from eyedrops.

Wish I had access to the full study. The finding/summary points are such important things to keep in mind. I find myself getting more and more routinely concerned about potential harm from overdoing pharmaceutical dry eye therapies. Obviously there is no clear-cut answer to determining what's causing what - but there is good solid reason to go slow, not do too much at once, and observe carefully for changes.

Ocular surface damage by ophthalmic compounds.

To describe the changes of the ocular surface following chronic use of eye drop therapies. The possible pathogenetic mechanisms responsible for specific signs and symptoms are described and discussed.

Topical treatments for ocular diseases may trigger an inflammatory response in predisposed patients, with local activation of immune cells and ocular surface damage. The resulting clinical picture may vary substantially, from mild to severe, sharing a red eye as a hallmark presentation. Recent in-vitro, in-vivo, and clinical data suggest that these detrimental effects are not solely related to eye drop preservatives and may be caused by the medication itself, especially for patients with preexisting ocular diseases. However, no specific tests are currently available to make a clear cut diagnosis between what is caused by the disease and what is the effect of its therapy. Patients' history and clinical features remain essential to hypothesize the underlying pathogenetic mechanism.

Topical therapies may induce ocular surface allergic reactions, dry eye-like reactions, and epithelial damage. Patients in need of chronic therapies are at higher risk of facing these detrimental effects of eye drop therapies and should be treated with unpreserved compounds.

Curr Opin Allergy Clin Immunol. 2011 Aug 4. [Epub ahead of print]
Mantelli F, Tranchina L, Lambiase A, Bonini S.
aDepartment of Ophthalmology, Campus Bio-Medico, University of Rome bDepartment of Biopathology, Ophthalmology Division, UOSD Glaucoma, University of Rome 'Tor Vergata', Rome, Italy.

Abstract: Scleral lenses in SJS

I find this sort of thing (90% success of SJS patients adapting to scleral lenses?!) very hopeful. One of the reasons people are so reluctant to try sclerals is that it seems counterintuitive to put a big lens in a dry eye. However, the results over the years show many people with very severe dry eye wearing them successfully. I'd really like to know how the 7 patients in this study fare a couple of years on - whether they're all wearing lenses full time.

To evaluate the efficacy of scleral contact lenses use on the management of ocular sequelae from Stevens-Johnson syndrome patients.

In a retrospective study, patients who suffered sequelae of Stevens-Johnson syndrome and started the use of scleral contact lenses were followed. Patients were submitted to an evaluation of symptoms through a questionnaire; ophthalmologic exam (visual acuity measurement, biomicroscopy, ocular surface staining with fluorescein drops, Schirmer test).

Ten eyes of seven patients were analyzed. Visual acuity varied from hand movements to 20/25. All patients presented some degree of corneal opacity and slight symblepharon. In patients whose adaptation to scleral contact lenses was successful (90%), they all refered improvement of symptoms and sight. As for the biomicroscopic findings it was observed an improvement of conjunctival hyperemia and keratitis and a reduction of the mucous secretion in 90% the cases.

A successful adaptation to scleral contact lenses was feasible on most patients, with relief of symptoms and better visual acuity, probably due to regularization of the surface. Scleral contact lenses represent an important and accessible alternative to reduce the limitations inferred by the damages from Stevens-Johnson syndrome.

Arq Bras Oftalmol. 2010 Oct;73(5):428-32.
[Scleral contact lens for ocular rehabilitation in patients with Stevens-Johnson syndrome].
[Article in Portuguese]
Siqueira AC, Santos MS, Farias CC, Barreiro TR, Gomes JÁ.
Departamento de Oftalmologia, Instituto da Visão, Universidade Federal de São Paulo, SP, Brasil.

Abstract: Neural basis of spontaneous blinks

Only sort of tangentially related to dry eye but I found this interesting... bearing in mind the chicken-and-egg relationship between dry eye and blinking.

Characterizing the spontaneous blink generator: an animal model.

Although spontaneous blinking is one of the most frequent human movements, little is known about its neural basis. We developed a rat model of spontaneous blinking to identify and better characterize the spontaneous blink generator. We monitored spontaneous blinking for 55 min periods in normal conditions and after the induction of mild dry eye or dopaminergic drug challenges. The normal spontaneous blink rate was 5.3 ± 0.3 blinks/min. Dry eye or 1 mg/kg apomorphine significantly increased and 0.1 mg/kg haloperidol significantly decreased the blink rate. Additional analyses revealed a consistent temporal organization to spontaneous blinking with a median 750 s period that was independent of the spontaneous blink rate. Dry eye and dopaminergic challenges significantly modified the regularity of the normal pattern of episodes of frequent blinking interspersed with intervals having few blinks. Dry eye and apomorphine enhanced the regularity of this pattern, whereas haloperidol reduced its regularity. The simplest explanation for our data is that the spinal trigeminal complex is a critical element in the generation of spontaneous blinks, incorporating reflex blinks from dry eye and indirect basal ganglia inputs into the blink generator. Although human subjects exhibited a higher average blink rate (17.6 ± 2.4) than rats, the temporal pattern of spontaneous blinking was qualitatively similar for both species. These data demonstrate that rats are an appropriate model for investigating the neural basis of human spontaneous blinking and suggest that the spinal trigeminal complex is a major element in the spontaneous blink generator.

J Neurosci. 2011 Aug 3;31(31):11256-67.
Kaminer J, Powers AS, Horn KG, Hui C, Evinger C.
Department of Psychology, Program in Neuroscience, and Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, New York 11794-5230, and SUNY Eye Institute.

Abstract: DA-HSV to diagnose dry eye

Nothing exciting here. When a diagnostic device has something intelligent and reproducible to say about severity levels, then it almost starts to get interesting.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy.

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area high-speed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring's regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion, this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

J Biomed Opt. 2011 Jul;16(7):076012.
Alonso-Caneiro D, Turuwhenua J, Iskander DR, Collins MJ.
Queensland University of Technology, School of Optometry, Victoria Park Road, Kelvin Grove, QLD 4059 Brisbane, AustraliaAuckland Bioengineering Institute and the Department of Optometry and Vision Science, University of Auckland, Auckland, New ZealandInstitute of Biomedical Engineering and Instrumentation, Plac Grunwaldzki 13, 50-377 Wroclaw, Poland.

Abstract: FD-OCT measurement of tear meniscus

Tear meniscus ain't everything, not by a long shot, but still... those who complain their eyes feel the same 5 minutes after putting in drops could understandably be tempted to think this explains how they feel.

Serial Measurement of Tear Meniscus by FD-OCT After Instillation of Artificial Tears in Patients With Dry Eyes.

To use Fourier-domain optical coherence tomography (FD-OCT) to study the effect of artificial tears on the tear meniscus in patients with dry eyes.

The lower tear meniscus of 16 consecutive patients with dry eyes was imaged by an FD-OCT system (RTVue; Optovue, Inc., Fremont, CA). Baseline and five serial pairs of measurements were taken after the instillation of artificial tears (Optive; Allergan, Irvine, CA) at 1, 2, 5, 10, and 15 minutes. The lower meniscus height, depth, and area were measured with a computer caliper.

Baseline meniscus measurements were 235.5 ± 150.0 μm, 138.1 ± 78.7 μm, and 0.020 ± 0.022 mm(2) for height, depth, and area, respectively. After instillation of artificial tears, all lower tear meniscus parameters remained significantly elevated for 5 minutes and returned to baseline by 10 minutes.

FD-OCT is able to quantify a dramatic initial increase in tear meniscus, followed by a decay back to baseline values after approximately 5 minutes. FD-OCT may be useful in objectively quantifying the dynamic efficacy of dry eye treatments.

Ophthalmic Surg Lasers Imaging. 2011 Jul-Aug;42(4):308-13. doi: 10.3928/15428877-20110603-02.
Bujak MC, Yiu S, Zhang X, Li Y, Huang D.

Drug updates: Disappointing Remura results

SeekingAlpha says:

Executives blamed a “dramatic” placebo response

Jeepers creepers, if that ain't a lesson in attempting to spin the unspinnable. Sigh. Let's hope the EAST study (see below) fares better.

ISTA Pharmaceuticals Reports Results From the First of Two Trials in the REMURA(TM) Phase 3 Clinical Program for Dry Eye Disease

IRVINE, CA, Jul 28, 2011 (MARKETWIRE via COMTEX) -- ISTA Pharmaceuticals, Inc. ISTA +11.29% , today announced top-line results from the first of its two Phase 3 studies to evaluate the short-term safety and efficacy of two concentrations of REMURA(TM) (bromfenac ophthalmic solution for dry eye) in alleviating the signs and symptoms of dry eye disease. The company's Phase 3 safety and efficacy program, which consists of two studies known as EAST and WEST, is being conducted under a Special Protocol Assessment (SPA) agreed upon with the U.S. Food and Drug Administration (FDA). Today's top-line results are from the WEST study; the EAST study is now fully enrolled and the Company expects to announce top-line results from the EAST study during fourth quarter of 2011.

According to preliminary analysis of the top-line results from the WEST study, while REMURA was highly effective in treating a sign and symptom of dry eye, it was not statistically significantly better than placebo, a common outcome reported in studies testing other dry eye therapies. From baseline, both concentrations of REMURA and the placebo showed highly statistically significant improvement (p < 0.0001) in one sign and one symptom. The co-primary end-points identified in the SPA require REMURA to achieve a statistically significant difference from placebo, not baseline, which was not achieved in the WEST Study.

In analyzing the patient data, the higher concentration of REMURA achieved statistical significance against placebo in the sign of conjunctival staining as measured using the Lissamine Green (LG) Staining test among a sub-population of female patients 51-70 years of age with moderate dry eye disease. Safety data demonstrated REMURA was well-tolerated, with an adverse event profile similar to placebo and consistent with those observed previously with REMURA in a Phase 2 study and with other prescription dry eye drops. All three formulations were rated by patients as very comfortable.

"Consistent with our Phase 2 Study data, today's results show REMURA has a significant impact on the signs and symptoms of dry eye when compared to baseline. Since REMURA did not meet its co-primary end points in the WEST study, armed with this data, we expect to amend the statistical plan to appropriately focus the EAST study," stated Timothy R. McNamara, Pharm.D., Vice President of Clinical Research and Medical Affairs of ISTA Pharmaceuticals. "The EAST study is now fully enrolled, but the database has not been locked. We continue to analyze the WEST data, and once we see the data from the EAST Study, which we plan to announce in the fourth quarter, we'll make decisions about future development plans."

Drug updates: RGN-259 starting (another?) Phase 2 trial

RegeneRx to start RGN-259 Phase 2 trial
July 29

US based drug developer RegeneRx Biopharmaceuticals has decided to start a placebo-controlled, double-masked Phase 2 trial for evaluating the efficacy and safety of RGN-259 in patients with dry eye syndrome soon.

The trial which will be conducted by ORA, an ophthalmic contract research organization, will start patient enrollment in next month.

In the trial, the patients will be given RGN-259 or placebo twice daily for 30 days.

Previously, RGN-259 has demonstrated reduction in corneal damage associated with dry eye syndrome in two animal models when compared to both positive and negative controls.

RegeneRx president and CEO Finkelstein said they have received Institutional Review Board approval for the trial, completed manufacturing of RGN-259 and placebo, and are currently preparing for enrollment of the first patients.

"This is a very important clinical trial for RegeneRx that is based on a body of human and preclinical data that suggest RGN-259 could have beneficial effects in treating dry eye," Finkelstein said.

Abstract: About tear lipocalins

Tear lipocalin: structure and function.

Lipocalins are a family of diverse low molecular weight proteins that act extracellularly. They use multiple recognition properties that include 1) ligand binding to small hydrophobic molecules, 2) macromolecular complexation with other soluble macromolecules, and 3) binding to specific cell surface receptors to deliver cargo. Tear lipocalin (TLC) is a major protein in tears and has a large ligand-binding cavity that allows the lipocalin to bind an extensive and diverse set of lipophilic molecules. TLC can also bind to macromolecules, including the tear proteins lactoferin and lysozyme. The receptor to which TLC binds is termed tear lipocalin-interacting membrane receptor (LIMR). LIMR appears to work by endocytosis. TLC has a variety of suggested functions in tears, including regulation of tear viscosity, binding and release of lipids, endonuclease inactivation of viral DNA, binding of microbial siderophores (iron chelators used to deliver essential iron to bacteria), serving as a biomarker for dry eye, and possessing anti-inflammatory activity. Additional research is warranted to determine the actual functions of TLC in tears and the presence of its receptor on the ocular surface.

Ocul Surf. 2011 Jul;9(3):126-38.
Dartt DA.
From the Schepens Eye Research Institute and Harvard Medical School, Boston, MA.

Abstract: Mustard gas & dry eye

I know I'm a broken record but... anybody with severe enough dry eye to be considering tarsorrhaphy, AMT etc (per below) should be considered for PROSE/scleral referral or at least informed of this option before invasive surgeries.

Sulfur mustard-induced ocular surface disorders.

Sulfur mustard is a vesicant agent with severe irritating effects on living tissues, including skin, mucous membranes, eyes, and respiratory tract. The eyes are the most susceptible tissue to mustard gas effects, and varying degrees of ocular involvement are seen in 75% to 90% of exposed individuals. Most cases resolve uneventfully; however, a minority of exposed patients will have a continuous process, which manifests clinically either as a persistent smoldering inflammation (chronic form) or late-onset lesions appearing many years after a variable "silent" period (delayed form). Distinctive features common to most cases with chronic involvement include chronic blepharitis, meibomian gland dysfunction, dry eye, limbal ischemia, limbal stem cell deficiency, aberrant conjunctival vessels, corneal neovascularization, and secondary degenerative changes, including lipid and amyloid deposition and corneal irregularity, thinning and scarring. Most cases can be managed with conservative measures, eg, preservative-free artificial tears, lubricants, and topical steroids. Punctal plugs or punctal cauterization is helpful in moderate and severe forms of injury. Surgical modalities, including lateral or medial tarsorrhaphies, amniotic membrane transplantation, lamellar or penetrating keratoplasty, and stem cell transplantation have been used.

Ocul Surf. 2011 Jul;9(3):163-78.
Baradaran-Rafii A, Eslani M, Tseng SC.
From the Ophthalmic Research Center, Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences.

Abstract: SAR1118 in dogs

For those of you following SAR-1118 developments....

The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca (KCS) is characterized by inflammation and decreased production of tears containing increased levels of cytokines. The release occurs in the setting of conjunctival and lacrimal gland inflammation, potentially mediated by the interaction between lymphocyte function-associated antigen (LFA)-1, a cell surface protein found on lymphocytes, and its cognate ligand intercellular adhesion molecule (ICAM)-1. SAR 1118 is a novel LFA-1 antagonist and may be an effective therapeutic agent for the treatment of KCS. The following studies were performed to assess the in vitro activity of SAR 1118 and to evaluate the clinical efficacy of topical SAR 1118 for the treatment of idiopathic canine KCS.

Pharmacodynamics were assessed by measuring the ability of SAR 1118 to inhibit Jurkat T-cell binding with recombinant human ICAM-1 and to inhibit cytokine release from human peripheral blood mononuclear cells (PBMCs) stimulated by staphylococcal enterotoxin B. For the assessment of clinical efficacy, 10 dogs diagnosed with idiopathic KCS were treated with SAR 1118 1% topical ophthalmic solution three times daily for 12 weeks. Schirmer's tear test (STT) was used to measure tear production.

SAR 1118 demonstrated concentration-dependent inhibition of Jurkat T-cell attachment, inhibition of lymphocyte activation, and release of inflammatory cytokines, particularly the Th1, Th2, and Th17 T-cell cytokines IFN-γ, IL-2, and IL-17F, respectively. Mean STT values increased from 3.4 mm during week 1 to 5.8 mm at week 12 (P < 0.025). No SAR 1118-related adverse events were observed.

SAR 1118 appears to be an effective anti-inflammatory treatment for KCS. Additional studies are warranted to establish the efficacy of SAR 1118 for the treatment of KCS in humans.

Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. Print 2011 May.
Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA.
School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.

Article: Scleral lens fitting

...And in that same CLS issue there's a great article by Lynette Johns OD of Boston Foundation for Sight discussing scleral lens fitting on dry-eyed folks from the doctor's perspective:

Fitting Scleral Lenses for Ocular Surface Disease
Defining fitting goals and patient expectations is an important first step in managing OSD with sclerals.

The resurgence of scleral lenses in GP materials has opened up many opportunities for fitting complex corneas. In the setting of irregular astigmatism and keratectasias (keratoconus, keratoglobus, pellucid marginal degeneration, and post-laser-assisted in situ keratomileusis [LASIK] ectasia), many patients who were unable to be optimally fit with corneal GP lenses have another non-surgical alternative to consider. The use of scleral lenses to visually rehabilitate these patients is equally rewarding for both the patients and the providers, especially when surgery can be avoided....

Article: Corneal stem cells

Sorry I didn't post this sooner... made a note of it and never got to it. Back in July there was a really nice CLS article by Drs. Mastrota and Townsend on corneal stem cells... If you have run across my links to items on limbal stem cell deficiency (LSCD) now and then and want to better understand what that is, click on this and read the full article:

A Closer Look at Corneal Stem Cells
Early intervention by practitioners can prevent and aid treatment of limbal stem cell deficiency.

We would imagine that similar to most of us, you confidently assure uncomfortable patients who have a corneal abrasion that the injury will heal relatively quickly with a good chance that their vision will be uncompromised. We daily take for granted the remarkable architecture and exquisite processes that create and regenerate the optically clear cornea.

How does the cornea maintain itself? How do superficial corneal abrasions heal? Why does corneal staining go away? Why can a cornea become vascularized?....