Tuesday, June 7, 2011

Abstract: EGP-437 for dry eye

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial.

To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients.

The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.5 mA-min at 2.5 mA (DP 7.5, n = 41); 10.5 mA-min at 3.5 mA (DP 10.5, n = 37); or 10.5 mA-min at 3.5 mA (placebo, n = 25). Three CAE visits and 4 follow-up visits occurred over 3 weeks. Patients meeting enrollment criteria received iontophoresis in both eyes after the second CAE exposure (visit 3) and before the third CAE exposure (visit 5). Primary efficacy endpoints were corneal staining and ocular discomfort. Secondary endpoints included tear film break-up time, ocular protection index (OPI), and symptomatology.

The DP 7.5 and DP 10.5 treatment groups showed statistically significant improvements in signs and symptoms of dry eye at various time points; however, the primary endpoints were not achieved. The DP 7.5 treatment group exhibited statistically significant improvements in corneal staining (when comparing the differences between study entry and exit, 3 weeks, P = 0.039), OPI (immediately following the second treatment, P = 0.048) and ocular discomfort at follow-up visits (a week after the first treatment, P = 0.032; 24 hours after the second treatment, P = 0.0032). Treatment-emergent adverse events (AEs) were experienced by 87% of patients and were consistent across all treatment groups. Most AEs were mild and no severe AEs were observed.

Ocular iontophoresis of EGP-437 demonstrated statistically and clinically significant improvements in signs and symptoms of dry eye syndrome within a CAE model.

Clin Ophthalmol. 2011;5:633-43. Epub 2011 May 15.
Patane MA, Cohen A, From S, Torkildsen G, Welch D, Ousler GW 3rd.
Eyegate Pharmaceuticals, Inc, Waltham, MA, USA;

Abstract: Solute gradient in the tear meniscus

A solute gradient in the tear meniscus. II. Implications for lid margin disease, including meibomian gland dysfunction.

We have hypothesized previously that evaporation from the tears generates a solute gradient across the tear meniscus, which delivers hyperosmolar stress to the mucocutaneous junction (MCJ) of the lid margin. This is proposed as the basis for Marx's line, a line of staining with topically applied dyes that lies directly behind the MCJ. In this article, we consider the implications of this hypothesis for progressive damage to the lid margin as an age-related phenomenon, its amplification in dry eye states, and its possible role in the etiology of meibomian gland dysfunction (MGD). It is suggested that a hyperosmolar or related stimulus, acting behind the MCJ over a lifetime, promotes the anterior migration of the MCJ, which is a feature of the aging lid margin. This mechanism would be amplified in dry eye states, not only by reason of increased tear molarity at the meniscus apex but also by raising the concentration of inflammatory peptides at this site. This could explain the increased width and irregularity of Marx's line in dry eye. While the presence of stem cells at the lid margin may equip this region to respond to such stress, their depletion could be the basis of irreversible lid margin damage. It is further proposed, given the proximity of the MCJ to the meibomian gland orifices, that the solute gradient mechanism could play a role in the initiation of MGD by delivering hyperosmolar and inflammatory stresses to the terminal ducts and orifices of the glands. By the same token, the presence of a zone of increased epithelial permeability in this region may provide a back door route for the delivery of drugs in the treatment of MGD.

Ocul Surf. 2011 Apr;9(2):92-7.
Bron AJ, Yokoi N, Gaffney EA, Tiffany JM.
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK. Anthony.Bron@eye.ox.ac.uk

Abstract: Schirmer I plus phenol red in diagnosing Sjogrens dry eye

Combination between Schirmer I test and Phenol Red Thread as a rescue strategy for diagnosis of ocular dryness associated with Sjogren's syndrome.

To define a combination between Schirmer I and phenol red thread test (PRT) that improves the screening of patients with ocular sicca syndrome.

Materiels and methods:
The PRT test was performed before (PRT1) and after (PRT2) the Schirmer I test, in both eyes of 143 patients complaining of ocular dryness secondary to Sjögren's syndrome (SS) or Sicca Asthenia Polyalgia Syndrome (SAPS) (72 and 71 patients respectively), and in 40 control patients. Groups were matched by age and gender. After determining the best cut-off values using the ROC (Receiver Operating Characteristic) procedure, several combinations of PRT and Schirmer I were assessed to improve the predictive values of the procedure.

The best cut-off value for PRT2, estimated at 15mm, provided a satisfying match between sensitivity and specificity indexes (68% and 90% respectively), similar to those obtained with the Schirmer I test. If PRT1 alone was ineffective to screen SGS from control patients, the comparison between PRT 1 and PRT2 (so-called "delta-PRT") was found as a good marker to detect patients with persistent tear reflex. Interestingly, the combination of positive Schirmer I, PRT 2 and/or delta-PRT tests was found as highly predictive of severe ocular sicca syndrome.

The combination of Schirmer I and PRT test strongly improves the screening procedure to detect patients with ocular dryness related to Sjögren or SAPS syndrome. It could be more widely used in daily clinical practice, besides Schirmer I test, to optimize the work-up of patients presenting with dry-eye subjective signs.

Invest Ophthalmol Vis Sci. 2011 May 5. [Epub ahead of print]
De Monchy I, Gendron G, Miceli C, Pogorzalek N, Mariette X, Labetoulle M.
Ophthalmology Department Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre Cedex, FRANCE.

Abstract: Infrared thermal imaging to detect dry eye

Not much detail here, but diagnosing dry eye by surface temperature sounds kind of interesting.

Noncontact detection of dry eye using a custom designed infrared thermal image system.

Dry eye syndrome is a common irritating eye disease. Current clinical diagnostic methods are invasive and uncomfortable for patients. This study developed a custom designed noncontact infrared (IR) thermal image system to measure the spatial and temporal variation of the ocular surface temperature over a 6-second eye-open period. This research defined two parameters: the temperature difference value and the compactness value to represent the temperature change and the irregularity of the temperature distribution on the tear film. Using these two parameters, this study achieved discrimination results for the dry eye and the normal eye groups; the sensitivity is 0.84, the specificity is 0.83, and the receiver operating characteristic area is 0.87. The results suggest that the custom designed IR thermal image system may be used as an effective tool for noncontact detection of dry eye.

J Biomed Opt. 2011 Apr;16(4):046009.
Su TY, Hwa CK, Liu PH, Wu MH, Chang DO, Su PF, Chang SW, Chiang HK.
National Yang-Ming University, Institute of Biomedical Engineering,

Abstract: Artificial tears - how long they last vs effect on vision

This study looks at (more or less) how long artificial tears outlast the blurring they cause. For the types of drops studied, both are brief enough that I don't know why we should care that much....

Visual Effect and Residence Time of Artificial Tears in Dry Eye Subjects.

The purpose of this investigation was to examine the relationship between the visual effect (VE) and residence time (RT) of artificial tears (ATs) in dry eye subjects.

The VEs and RTs were measured after administration of 25 μl of an AT into the inferior fornix of 18 dry eye subjects. The VE was investigated by measuring contrast sensitivity before and after AT administration. The return to baseline sensitivity (RTBS) was taken as the time it took to return to within 1 SD of baseline contrast sensitivity. RT was measured using fluorescent formulations and a scanning fluorometer.

No correlation was found between RTBS and RT for a low viscosity (saline-F) and a medium viscosity AT (CMC-F; p > 0.05). There was a moderate correlation for a higher viscosity AT (PEG-F; p = 0.03). For all solutions, RT was significantly longer than RTBS (p < 0.001). There was a significant difference in RTBS between saline-F and PEG-F (p = 0.002) but not between saline-F and CMC-F (p = 0.87). There was a significant difference in RT between saline-F and both PEG-F and CMC-F (p < 0.001 and p = 0.018, respectively).

No correlation was found between RTBS and RT for saline-F or CMC-F (moderate correlation for PEG-F). These ATs are present on the eye for a significantly longer time than their adverse affect on vision. An ideal AT would result in minimal if any initial blur on instillation while remaining in the eye for an extended period of time.

Optom Vis Sci. 2011 Apr 28. [Epub ahead of print]
Hall JQ Jr, Ridder WH 3rd, Nguyen AL, Paugh JR.
*BS, BA †OD, PhD, FAAO ‡PhD Southern California College of Optometry, Fullerton, California (JQH, WHR, JRP), and California State University, Fullerton, California (ALN).

Abstract: Salivary gland & labial mucous membrane grafts in SJS dry eye

Minor salivary glands and labial mucous membrane graft in the treatment of severe symblepharon and dry eye in patients with Stevens-Johnson syndrome.

To evaluate minor salivary glands and labial mucous membrane graft in patients with severe symblepharon and dry eye secondary to Stevens-Johnson syndrome (SJS).

A prospective, non-comparative, interventional case series of 19 patients with severe symblepharon and dry eye secondary to SJS who underwent labial mucous membrane and minor salivary glands transplantation. A complete ophthalmic examination including the Schirmer I test was performed prior to and following surgery. All patients had a preoperative Schirmer I test value of zero.

Nineteen patients with severe symblepharon and dry eye secondary to SJS were included in the study. There was a statistically significant improvement in the best spectacle-corrected visual acuity in eight patients (t test; p=0.0070). Values obtained in the Schirmer I test improved significantly in 14 eyes (73.7%) 6 months following surgery (χ(2) test; p=0.0094). A statistically significant increase in tear production (Schirmer I test) was found in eyes that received more than 10 glands per graft compared with eyes that received fewer glands (χ(2) test; p=0.0096). Corneal transparency improved significantly in 11 (72.2%) eyes and corneal neovascularisation improved significantly in five eyes (29.4%) (McNemar test; p=0.001 and p=0.0005). The symptoms questionnaire revealed improvement in foreign body sensation in 53.6% of the patients, in photophobia in 50.2% and in pain in 54.8% (Kruskal-Wallis test; p=0.0167).

Labial mucous membrane and minor salivary glands transplantation were found to constitute a good option for the treatment of severe symblepharon and dry eye secondary to SJS. This may be considered as a step prior to limbal stem cell and corneal transplantation in these patients.

Br J Ophthalmol. 2011 Apr 27. [Epub ahead of print]
Sant'anna AE, Hazarbassanov RM, de Freitas D, Gomes JA.
Department of Ophthalmology, Federal University of São Paulo, SP, Brazil.

Abstract: New non-invasive pre-corneal tear film measurement

Pre-corneal tear film thickness in humans measured with a novel technique.

The purpose of this work was to gather preliminary data in normals and dry eye subjects, using a new, non-invasive imaging platform to measure the thickness of pre-corneal tear film.

Human subjects were screened for dry eye and classified as dry or normal. Tear film thickness over the inferior paracentral cornea was measured using laser illumination and a complementary metal-oxide-semiconductor (CMOS) camera. A previously developed mathematical model was used to calculate the thickness of the tear film by applying the principle of spatial auto-correlation function (ACF).

Mean tear film thickness values (±SD) were 3.05 μm (0.20) and 2.48 μm (0.32) on the initial visit for normals (n=18) and dry eye subjects (n=22), respectively, and were significantly different (p<0.001, 2-sample t-test). Repeatability was good between visit 1 and 2 for normals (intraclass correlation coefficient [ICC]=0.935) and dry eye subjects (ICC=0.950). Tear film thickness increased above baseline for the dry eye subjects following viscous drop instillation and remained significantly elevated for up to approximately 32 min (n=20; p<0.05 until 32 min; general linear mixed model and Dunnett's tests).

This technique for imaging the ocular surface appears to provide tear thickness values in agreement with other non-invasive methods. Moreover, the technique can differentiate between normal and dry eye patient types.

Mol Vis. 2011 Mar 22;17:756-67.
Azartash K, Kwan J, Paugh JR, Nguyen AL, Jester JV, Gratton E.

Abstract: Hyperosmolarity does not affect goblet cell population

Effect of tear hyperosmolarity and signs of clinical ocular surface pathology upon conjunctival goblet cell function in the human ocular surface.

To investigate the effect of tear hyperosmolarity and signs of clinical ocular surface pathology upon conjunctival goblet cell population.

111 participants were assessed using tear osmolarity (TO) measurements and a comprehensive selection of clinical ophthalmic tests. The resultant clinical database was assessed for evidence of patterns of composite increasing pathology. The total, filled, and empty goblet cell numbers were measured: total number of goblet cells as per cytokeratin 7 (CK7) immunofluorescence and number of filled goblet cells as per periodic acid Schiff's reagent (PAS) or lectin Helix Pomatia Agglutin (HPA). Goblet cell profile was correlated with composite clinical pathological grades.

No significant correlation was found between TO and goblet cell number or function (as indicated by number of filled or unfilled goblet cells). Distinct composite clinical pathological groups 0-IV with increasing pathology were created based upon the frequency of positive pathological signs, which adhered to the Dry Eye Workshop (DEWs) purported mechanism. Only in grade IV was there significantly increased mean tear osmolarity of 344 mOsm/L (p<0.000) along with significantly decreased empty goblet cell number (CK7+ and HPA-) compared to filled (CK7+ and HPA+, p=0.000). When the number of filled goblet cells (PAS+) was analyzed there was significant increase in tear osmolarity for the two most severe grades; 3 and 4.

The goblet cell population does not appear to be affected by isolated tear hyperosmolarity. Hyperosmolarity when combined with other ocular surface pathology or inflammation alter the goblet cell population.

Invest Ophthalmol Vis Sci. 2011 Apr 25. [Epub ahead of print]
Moore JE, Vasey GT, Dartt DA, Mc Gilligan VE, Atkinson SD, Grills C, Lamey PJ, Leccisotti A, Frazer DG, Moore TC.
Centre for Molecular Biosciences, University of Ulster, Coleraine, BT52 1SA.