Drug updates: Rebamipide

This is not new news, but I think I missed it along the way. Otsuka has applied for regulatory approval in Japan for Rebamipide following positive Phase III data, but is supposedly somewhere in Phase II in the US. Have not heard any positive noises about US prospects on this drug for a long time.

May 6 press release

Phase III Study Results for Rebamipide Ophthalmic Suspension for Dry Eye Announced at ARVO 2011

Tokyo, Japan, May 6, 2011 -- Otsuka Pharmaceutical Co., Ltd. today announced results of a phase III clinical study of its in-development dry eye treatment "rebamipide ophthalmic suspension" for dry eye patients, at ARVO* 2011 (May 1-5, 2011, Fort Lauderdale, Florida, USA).

* ARVO: Association for Research in Vision and Ophthalmology
The phase III study was conducted in Japan on 188 patients with signs and symptoms of dry eye, to examine the efficacy and safety of 2% rebamipide ophthalmic suspension in comparison with 0.1% sodium hyaluronate ophthalmic solution. As the results of the study, it was confirmed that in addition to the improvement in corneal-conjunctival damage in patients with dry eye, rebamipide ophthalmic suspension also showed improvements in subjective symptoms such as foreign body sensation and eye pain and in subject's overall treatment impressions.

Based upon the results of this study, in October 2010 Otsuka Pharmaceutical applied for regulatory approval to manufacture and market rebamipide ophthalmic suspension in Japan. In the U.S., a phase II program with co-development partner Acucela Inc. is ongoing.

Based on its corporate philosophy of "Otsuka-people creating new products for better health worldwide," Otsuka Pharmaceutical Co., Ltd. is dedicated to contributing to the health of people around the world.

About 5 weeks of updates to follow...

Sorry I've gotten so behind. The next several posts will be catching up on all June and even a little bit of May dry eye news.

Abstract: EGP-437 for dry eye

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

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

METHODS:
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.

RESULTS:
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.

CONCLUSION:
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.

Purpose:
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.

Results:
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.

Conclusion:
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.

PURPOSE.:
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.

METHODS.:
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.

RESULTS.:
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).

CONCLUSIONS.:
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.

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

Methods
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.

Results
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).

Conclusion
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.

PURPOSE:
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.

METHODS:
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).

RESULTS:
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).

CONCLUSIONS:
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.

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

Methods:
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.

Results:
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.

Conclusions:
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.

Dry eye drug clinical trials - updates

Please check out the newly updated dry eye drug clinical trial roster.

Items that have been updated recently -

Novagali's Cyclokat, which completed a phase III last year and mentioned positive results in a January press release, is headed into a new pivotal Phase III according to a May press release.

EyeGate Pharma's EGP-437 has completed a Phase III trial as of April, according to clinicaltrials.gov.

Ista's Remura (low dose Bromfenac) is in a Phase III presently, with results expected the latter half of this year according to the manufacturer's pipeline page.

Can-Fite Biopharma / CF-101: Oral A(3) adenosine receptor agonist. Approved for entering Phase III on Sept 5 2010 but not yet recruiting according to clinicaltrials.gov.

Allergan: Clinicaltrials.gov lists "EDNP" i.e. "eye drop new platform" in Phase III (being compared to Refresh) - and since the primary endpoint being evaluated is symptoms (OSDI) this is probably an OTC but that isn't quite clear. Allergan's site lists Restasis X in Phase II but no recent information on that at all.

ALCON: (1) DUREZOL: According to clinicaltrials.gov, Durezol is in a Phase II looking at its use specifically as an anti-inflammatory in dry eye patients. (2) ESBA105 (from acquisition of ESBATech in 2009), a biological, for severe dry eye, was added to clinicaltrials.gov in April 2011. (3) AL38583 (cyclosporine .05% or .10%) completed a Phase II last year but there hasn't been a peep out of it since then. Dark horse or dead in the water? Your guess is better than mine. (4) A last note on ex GSK Cilomilast and/or AL43546 - I don't know what's going on with these if anything (probably nothing) but I will drop these from the roster if I don't hear pretty soon.

Mimetogen / MIM-D3: Phase II ongoing, started recently.

SARCODE SAR1118: More data presented at ARVO in May 2011. Presumably this is from the study that was completed about this time last year.

SANTEN / DE110: Added to list May 2011 based on clinicaltrials.gov listing. Not sure what this is.

Abstracte: Phospholipid transfer protein and the tear fluid

Dry Eye Symptoms Are Increased in Mice Deficient in Phospholipid Transfer Protein (PLTP).

In the tear fluid the outermost part facing the tear-air interface is composed of lipids preventing evaporation of the tears. Phospholipid transfer protein (PLTP) mediates phospholipid transfer processes between serum lipoproteins and is also a normal component of human tears. To study whether PLTP plays any functional role in tear fluid we investigated PLTP-deficient mice, applying functional and morphologic analyses under normal housing and experimentally induced dry eye conditions. Aqueous tear fluid production, corneal epithelial morphology, barrier function, and occludin expression were assessed. In mice with a full deficiency of functional PLTP enhanced corneal epithelial damage, increased corneal permeability to carboxyfluorescein, and decreased corneal epithelial occludin expression were shown. These pathologic signs were worsened by experimentally induced dry eye both in wild-type and PLTP knock-out mice. Deficiency in the production of tear PLTP in mice is accompanied by corneal epithelial damage, a feature that is typical in human dry eye syndrome (DES). To complement animal experiments we collected tear fluid from human dry eye patients as well as healthy control subjects. Increased tear fluid PLTP activity was observed among DES patients. In conclusion, the presence of PLTP in tear fluid appears to be essential for maintaining a healthy and functional ocular surface. Increased PLTP activity in human tear fluid in DES patients suggests an ocular surface protective role for this lipid transfer protein.

Am J Pathol. 2011 May;178(5):2058-65.
Setälä NL, Metso J, Jauhiainen M, Sajantila A, Holopainen JM.
Source
Department of Ophthalmology, University of Helsinki, Helsinki, Finland; Department of Ophthalmology, University of Turku, Finland; National Institute for Health and Welfare and Institute for Molecular Medicine, Biomedicum, Helsinki, Finland.

Abstract: Dry eye in GvHD

Looks at frequency of dry eye and other ocular complications from chronic GvHD in a patient population in Pakistan.

Frequency of ocular manifestations of chronic graft versus host disease.

BACKGROUND:
With the advancement of techniques for haematopoietic cell transplantation, the number of transplant survivors is increasing rapidly and so are the chances of chronic graft versus host disease (cGVHD). The ocular manifestations of this disease have not been explored in our local population. This study was conducted to determine the frequency of ocular complications in cases of cGVHD following successful bone marrow transplantation.

METHODS:
Twelve diagnosed cases of cGVHD were evaluated from June 2008 to March 2009 and there ocular manifestations were noted especially the ocular surface disorders, using double staining method with fluorescein and rose-bengal.

RESULTS:
Nine patients (75%) were having dry eyes, 7 (58.3%) with mebomian glands dysfunction, 4 (33%) with acute conjunctivitis, 2 (16.7%) with bilateral lacrimal canalicular occlusion, and 1 (8.3%) each of bilateral posterior subcapsular cataract, unilateral sterile corneal epithelial defect, anterior uveitis, retinal haemorrhages and disc oedema.

CONCLUSION:
The higher frequency of dry eyes along with other ocular manifestations in patients of cGVHD suggests the need of close ophthalmic monitoring in all such cases.

J Ayub Med Coll Abbottabad. 2010 Jan-Mar;22(1):80-3.
Arain MA, Niazi MK, Khan MD, Ahmed P, Naz MA, Fayyaz M.
Armed Forces Institute of Ophthalmology, Rawalpindi. doctorarain@yahoo.com

Abstract: Mouse lacrimal cell study

I'm not going to attempt to summarize something this technical, but I do love this sort of thing. When i'm done tripping over the terminology and prowling through wikipedia to get a better sense of it, I'm just in such awe of the complexity and beauty of our tear production system. We are fearfully and wonderfully made.

Polycystin-2 expression and function in adult mouse lacrimal acinar cells.

Purpose:
Lacrimal glands regulate the production and secretion of tear fluid. Dysfunction of lacrimal gland acinar cells can ultimately result in ocular surface disorders, such as dry-eye disease. Ca(2+) homeostasis is tightly regulated in the cellular environment, and secretion from the acinar cells of the lacrimal gland is regulated by both cholinergic and adrenergic stimuli, which both result in changes in the cytosolic Ca(2+) concentration. We have previously described the detailed intracellular distribution of IP(3)Rs and RyRs in lacrimal acinar cells, however, little is known regarding the expression and distribution of the third major class of intracellular Ca(2+) release channels, transient receptor potential polycystin family (TRPP) channels.

Methods:
Studies were performed in adult lacrimal gland tissue of Swiss-Webster mice. Expression, localization and intracellular distribution of TRPP Ca(2+) channels were investigated using immunocytochemistry, immunohistochemistry and electron microscopy. The biophysical properties of single polycystin-2 channels were investigated using a planar lipid bilayer electrophysiology system.

Results:
All channel-forming isoforms of TRPP channels (polycystin-2, polycystin-L and polycystin-2L2) were expressed in adult mouse lacrimal gland. Subcellular analysis of immunogold labeling revealed strongest polycystin-2 expression on the membranes of the endoplasmic reticulum, Golgi and nucleus. Biophysical properties of lacrimal gland polycystin-2 channels were similar to those described for other tissues.

Conclusions:
The expression of TRPP channels in lacrimal acinar cells suggests a functional role of the proteins in the regulation of lacrimal fluid secretion under physiological and disease conditions, and provides the basis for future studies focusing on physiology and pharmacology.

Invest Ophthalmol Vis Sci. 2011 Apr 20. [Epub ahead of print]
Kaja S, Hilgenberg JD, Rybalchenko V, Medina-Ortiz WE, Gregg EV, Koulen P.
Vision Research Center and Departments of Ophthalmology and Basic Medical Science, University of Missouri - Kansas City, School of Medicine, Kansas City, MO.

Abstract: Reduced goblet cell density in dry eye patients

This study, originating in Nepal of all places, is not original and not news, but it's a useful reminder that dry eyes are not just about meibomian and/or lacrimal gland dysfunction. There's the mucin issue as well - which depends on goblet cell density. Of late most of the chatter and technological developments seem to be focused on the meibomian glands. They are nice low hanging fruit (so to speak) and it's easy to understand why treating them has come into vogue. It's not really all that hard to get clinical improvement, at the end of the day. And the attention MGs are getting truly is long overdue.

And yet...

Where oh where is the PAIN coming from? When I think of the people doing all these glamorous boutique MGD treatments and not experiencing conclusive, lasting symptomatic improvement it makes me gnash my teeth.

We still really don't know our chickens from our eggs in the world of dry eye. Let's keep goblet cells and mucous in mind.

The conjunctival impression cytology between the diagnosed cases of dry eye and normal individuals.

Background:
The dry eye or tear film dysfunction is a common ophthalmic syndrome.

Objective:
To compare the results of conjunctival impression cytology between dry eye patients and normal individuals.

Subjects and methods:
A case control study including consecutive cases of dry eye syndrome was carried out. Individuals without dry eye were taken as control. Impression of conjunctiva with cellulose acetate filter paper was taken from inferonasal bulbar conjunctiva and was stained with Periodic Acid- Schiff (PAS) and counter-stained with haematoxylin and eosin. Main outcome measure: goblet cell density.

Results:
There was a female preponderance in dry eye disease. Of 114 dry eye cases, 49.2% eyes showed decreased or absent goblet cell density. In 72 normal individuals 73.7% eyes showed normal goblet cell density and 26.3% of eyes showed decreased or absent goblet cells (p less than 0.001). The tear break-up time (TBUT) test was significantly more likely to be less than 10 seconds in cases as compared to the controls ( OR = 19.36, 95% CI = 7.56 - 52.52). Similarly, the goblet cell density was likely to be significantly reduced in cases with dry eye syndrome (OR= 2.25, 95% CI = 1.26 - 4.02, p = 0.003).

Conclusion:
Goblet cell density significantly reduces in dry eye syndrome. The impression cytology is a useful test for the diagnosis of dry eye syndrome. Key words: impression cytology; conjunctiva; dry eyes; tear film.

Nepal J Ophthalmol. 2011 Jan;3(5):39-44. doi: 10.3126/nepjoph.v3i1.4277.
Shrestha E, Shrestha JK, Shayami G, Chaudhary M.
Consultant Ophthalmologist, Himalaya Eye Hospital, Pokhara, Nepal.