Thursday, March 4, 2010

LASIK in the news again...

End of a long day... sclerals sitting in their case... here I sit, gritting my teeth while trying to motivate myself to write some commentary about the recent ABC interview of Morris Waxler (former FDA chief responsible during the period excimer lasers were first being approved... and who awhile back testified against a manufacturer that was sued and later investigated by the FDA for failing to report complications it knew of) as he discussed concerns about the inadequacy of the FDA's safety review back in the beginning.

But before I could lay hands on a link to the article, I ran across a more recent response to it from a refractive surgeon that made me squirm so much I actually wrote in a response.

Here's the article:

An Eye Doctor's Counterpoint
Tuesday, March 02, 2010
By Dr. John P. Frangie
Some two years ago, I was troubled and disappointed as I read Abby Ellin’s article in the New York Times. Her story—the tale of an intelligent patient who carried out her due diligence, selected a well-trained and capable surgeon, only to experience a poor outcome—embodied a tragedy to an ophthalmologist who helped collect data for the FDA laser correction trials.

Ellin’s latest article in the Advocate is timely, as the FDA is again scrutinizing the safety and efficacy of LASIK (an eponym for laser assisted in situ keratomileusis). Coincidentally, Good Morning America also had a feature regarding LASIK safety on February 25, 2010 (http://abcnews.goGMA/OnCall/lasik-surgery-side-effects-fda-regulator/story?id=9933008).

Ellin’s writings, and the FDA‘s investigation, underscore a number of important points. First and foremost, LASIK is a surgical procedure; as such, it has attendant risks, and no surgeon is able to unequivocally “guarantee” the results. Complications may occur—even in the most skilled hands, utilizing the most advanced technology. These complications may have long-lasting or even permanent implications.

The Advocate article by Ellin also mentions that she signed an informed consent, but in retrospect, she did not truly realize or envision the impact and extent of the potential problems that she has had to endure. There is a plethora of ethical and medicolegal treatises which document and debate the informed consent process. The question which is inevitably raised is, Can a lay person truly give complete, informed consent where they are cognizant of the risks and implications of those risks upon their life?

I have no qualms with points made by Good Morning America and Ellin, but I believe their reports could offer more balance.
Allow me to offer a few observations:

Relatively few patients experience the complications of dry-eye, glare and halos after LASIK.

Okay... stop RIGHT THERE. Relatively few? You lost me. It's just not true. Even the medical literature says so - at least, in such of the peer-reviewed journals as are not industry mouthpieces.

The Good Morning America feature does acknowledge the overwhelming success rates of LASIK
It is not accurate to compare the outcomes of LASIK procedures performed five years ago (and certainly not 12 years ago) to those offered today, as many advances in the technology and understanding of laser correction have been made. For instance, most LASIK flaps in the United States today are not created with a blade— the major cause of ocular dryness and flap complications prior to 2003....

The way this is phrased seems to imply that so long as a microkeratome isn't used, this won't happen to you. Problem one.

Second, what is this ostensible obsolence of microkeratomes based upon? Nonsense. Show me some statistics. Microkeratomes are still widely used - often the same surgeon uses both techniques.

I think this reference to "prior to 2003" is rather devious. You mean microkeratome flaps were the problem... only up to 2003? That's when it was barely launched. I was alive and well in 2003 and I know as well as you do that surgeons weren't stampeding to lay down $500k for an Intralase the moment they hit the market. It took years for them to even get a significant chunk of the market for that technology. Obsolescence is a long ways off.

Besides, um... us millions who WERE lasered in the last 15 years of microkeratomes, plus the rest that will be in future years till microkeratomes become obsolete (if they do), what are we, chopped liver?

In summary, LASIK is one of the safest, most effective surgical procedures performed, with a constantly improving safety and efficacy profile. Despite this, the patient must keep in mind that it is a surgical procedure with potential risks. LASIK is an elective procedure, and therefore affords one the luxury of time—to meet with your surgeon, express your concerns and goals and have your questions addressed. Your physician will give you an informed consent document. Bring it home and read it at your leisure; if you have questions, ask them before the day of your treatment. It is important that one is comfortable with the surgeon, the procedure, and the decision to proceed. While hindsight is 20/20, moving forward with your eyes open will serve you well.

These elegant little summary statements sound eminently reasonable to everyone except those who, after experiencing complications without receiving adequate treatments, come to realize that asking the questions is only useful if the answers are grounded in practical reality from the patient's point of view rather than the doctor's.

I might as well post here my response to the article.

Dr. Frangie,

You state in this article, "Relatively few patients experience the complications of dry-eye...after LASIK".

This statement is not supported by the medical literature. Medical studies abound suggesting rates in the neighborhood of 5%, 10%, 20%, and at least one as high as 36%, employing a variety of methods assessing signs and/or symptoms. By any credible measure of ocular surface disease symptoms, the incidence of post LASIK dry eye is more than a little significant. Dry eye is in fact well known to be the most frequently occurring complication after LASIK - as is stated in the majority of informed consent forms that I have seen over the years, though most do not go so far as to explain the potential severity or persistence of this condition or possibility of available treatments not sufficing.

Everyone in the ophthalmic pharmaceutical industries know that LASIK dry eye is a big deal. New products have been developed specifically for people with LASIK dry eye. The cat has been out of the proverbial bag too long to make statements downplaying the significance of post LASIK dry eye.


Rebecca Petris

Abstract: MGD screening in Singapore

Screening for Meibomian Gland Disease: Its Relation to Dry Eye Subtypes and Symptoms in a Tertiary Referral Clinic in Singapore.
Invest Ophthalmol Vis Sci. 2010 Feb 24. [Epub ahead of print]
Tong L, Chaurasia SS, Mehta JS, Beuerman RW.
Cornea and external eye disease, Singapore National Eye Center, Singapore, Singapore.

Background/aims: To study screening methods and associated factors of Meibomian gland disease and dry eye subtypes in a specialized eye clinic in Singapore.

Methods: This cross-sectional study involved 200 patients in a dry eye clinic and the outcome measures evaluated are Dysfunctional Tear Syndrome (DTS) level, Meibomian Gland Disease grade, Schirmer's test (ST), fluorescein tear break up time (TBUT), corneal fluorescein staining grade, and irritative eye symptoms.

Results: The Meibomian gland screening grade was associated with TBUT (p=0.007), especially in the upper eyelid, and correlated to reading difficulty (p=0.007), and reversibility of symptomatic blurring with lubricants (p=0.006). Abnormal ST was associated with early morning discomfort (p=0.001) and reduced TBUT was linked to discomfort in windy conditions (p<0.001). In all patients examined, evaporative dry eye (58%) was most common, followed by mixed evaporative and aqueous tear deficiency (30.5%) types. Fluorescein staining in the central and inferior cornea was most severe in the mixed type.

Conclusions: In dry eye patients, screening for Meibomian gland disease based on anteriorisation of Marx's line may predict decrease in TBUT and difficulties performing certain visual-function related activities. This facilitates better understanding of the Meibomian gland's contribution to multi-factorial dry eye syndrome, apart from routine conventional tests performed in clinics.

Abstract: Techniques for assessing lower tear meniscus height

Clinical assessment of the lower tear meniscus height.
Ophthalmic Physiol Opt. 2009 Sep;29(5):487-496. Epub 2009 Jun 30.
García-Resúa C, Santodomingo-Rubido J, Lira M, Giraldez MJ, Vilar EY.
Department of Applied Physics (Optometry Group), University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.

PURPOSE: Different values of the lower tear meniscus height (TMH) can be obtained depending on the method and technique of measurement employed. This study aimed to assess (1) differences between the absolute (TMH-A), reflex (TMH-R) and fluorescein (TMH-F) lower tear meniscus heights, (2) differences between the central (TMH-R), nasal (TMH-RN) and temporal (TMH-RT) reflex lower tear meniscus heights and (3) the amount of fluorescein present in the lower tear meniscus, 5 min after fluorescein instillation (TMH-FV).

METHODS: Thirty four young healthy subjects were included in the study. The lower tear meniscus height (TMH) was measured using an eye piece graticule inserted into a slit-lamp.

RESULTS: Mean +/- S.D. values of TMH-A, TMH-R, TMH-RN, TMH-RT, TMH-F and TMH-FV of 0.25 +/- 0.08, 0.13 +/- 0.05, 0.23 +/- 0.06, 0.21 +/- 0.05, 0.27 +/- 0.11 and 0.004 +/- 0.001 mm, respectively were found. The TMH-R was significantly lower than the TMH-A and the TMH-F (p < 0.0001). The TMH-RN and TMH-RT were significantly higher than the TMH-R (p < 0.0001). The TMH-F was significant higher than the TMH-FV (p < 0.0001). No significant differences were found between the TMH-A and TMH-F (p = 0.2), and between the TMH-RN and TMH-RT (p = 0.36).

CONCLUSION: Careful instillation of fluorescein does not affect normal TMH values. Fluorescein is washed out from the lower tear meniscus 5 min after instillation. Higher values of the TMH can be found at nasal and temporal locations compared to the center of the lower eye lid.

Abstract: How primary care deals with red eyes

Diagnosis and management of red eye in primary care.
Am Fam Physician. 2010 Jan 15;81(2):137-44.
Cronau H, Kankanala RR, Mauger T.
Department of Family Medicine, The Ohio State University College of Medicine, Columbus, OH 43210 , USA.
Summary for patients in:
Am Fam Physician. 2010 Jan 15;81(2):145.

Red eye is the cardinal sign of ocular inflammation. The condition is usually benign and can be managed by primary care physicians. Conjunctivitis is the most common cause of red eye. Other common causes include blepharitis, corneal abrasion, foreign body, subconjunctival hemorrhage, keratitis, iritis, glaucoma, chemical burn, and scleritis. Signs and symptoms of red eye include eye discharge, redness, pain, photophobia, itching, and visual changes. Generally, viral and bacterial conjunctivitis are self-limiting conditions, and serious complications are rare. Because there is no specific diagnostic test to differentiate viral from bacterial conjunctivitis, most cases are treated using broad-spectrum antibiotics. Allergies or irritants also may cause conjunctivitis. The cause of red eye can be diagnosed through a detailed patient history and careful eye examination, and treatment is based on the underlying etiology. Recognizing the need for emergent referral to an ophthalmologist is key in the primary care management of red eye. Referral is necessary when severe pain is not relieved with topical anesthetics; topical steroids are needed; or the patient has vision loss, copious purulent discharge, corneal involvement, traumatic eye injury, recent ocular surgery, distorted pupil, herpes infection, or recurrent infections.

Abstract: Carbomer vs. hydroxypropyl-guar (artificial tears)

Aaaaaand it's a tie. Took the prize for longest study title though.

Clin Ther. 2010 Jan;32(1):44-52.
Comparison of the clinical effects of carbomer-based lipid-containing gel and hydroxypropyl-guar gel artificial tear formulations in patients with dry eye syndrome: a 4-week, prospective, open-label, randomized, parallel-group, noninferiority study.
Wang TJ, Wang IJ, Ho JD, Chou HC, Lin SY, Huang MC.
Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan; Department of Ophthalmology, Taipei Medical University, Taipei, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.

BACKGROUND: Most marketed artificial tears are substitutes for the aqueous layers of the tear film; therefore, frequent instillation of artificial tears is necessary. Newer gel-, cellulose-, and mineral oil-based formulations have been designed to overcome the disadvantages of current aqueous tear substitutes by offering prolonged retention times.

OBJECTIVES: The aim of this study was to compare the efficacy, safety, and local tolerance of artificial tears containing carbomer-based lipids or hydroxypropyl (HP)-guar gel in patients with dry eye syndrome.

METHODS: A 4-week, prospective, randomized, parallel-group, comparative, noninferiority study was conducted at the Taipei Medical University Hospital (Taipei, Taiwan) in patients with dry eye syndrome who were randomly assigned to 1 of 2 treatment groups: the carbomer-based lipid-containing (CBLC) gel group and the HP-guar gel group. The primary end point was global assessment of study treatment by the patients at weeks 2 and 4. All patients met the diagnostic criteria of impaired tear function and ocular surface abnormalities. Outcomes measured at baseline and 2 and 4 weeks included Schirmer's test values, tear breakup time (TBUT), and a patient subjective assessment of symptoms. Safety and tolerability were assessed by clinically significant changes in terms of incidence of adverse events and conducted by unmasked investigators.

RESULTS: A total of 30 Taiwanese patients with dry eye syndrome were included and randomly assigned to the 2 treatment groups: the mean (SD) age was 40.37 (14.96) years in the CBLC gel group and 49.49 (12.20) years in the HP-guar gel group. At baseline, the mean (SD) Schirmer's test value was 4.53 (2.28) mm in the right eye and 5.13 (2.42) mm in the left eye in the CBLC gel group; 4.40 (2.16) mm in the right eye and 4.20 (1.78) mm in the left eye for the HP-guar gel group. The mean (SD) for both eyes was 4.83 (2.36) mm in the CBLC gel group and 4.30 (2.08) mm in the HP-guar gel group. There was no statistically significant difference between Schirmer's scores at baseline. Patients in both treatment groups experienced an improvement from baseline in symptoms and signs, Schirmer's test value, and TBUT at 2 and 4 weeks after treatment. The Schirmer's test score increased to a mean of 8.20 (4.49) mm in the right eye and 9.33 (4.94) mm in the left eye in the CBLC gel group after 2 weeks, and increased to 10.07 (5.56) mm in the right eye and 10.86 (5.58) mm in the left eye after 4 weeks. The increases in Schirmer's test score and TBUT were also observed in the HP-guar gel group. The Schirmer's test score increased to 5.13 (2.18) mm in the right eye and 5.60 (2.74) mm in the left eye after 2 weeks, and increased to 6.93 (3.37) mm in the right eye and 6.53 (3.16) mm in the left eye after 4 weeks. The increase in Schirmer's test values in both eyes was significantly greater at 2 and 4 weeks in the CBLC gel group than that in the HP-guar gel artificial tear group (all, P < 0.05). Subjective patient assessment was better with the CBLC group (excellent and good reported by 26.6% and 73.4%, respectively, of the CBLC gel group vs 13.4% and 33.4% of the HP-guar gel group at 4 weeks; both, P = 0.004).

CONCLUSIONS: Both artificial tear formulations were effective in relieving dry eye syndrome in these patients. The tolerance of CBLC gel artificial tears was comparable to that of HP-guar gel artificial tears.

Wednesday, March 3, 2010

Newsblurb: Workers comp victory for a dry eye patient

Appeals court upholds comp benefits for worker in Iraq

NEW YORK—Substantial evidence exists to find that a truck driver who worked in Iraq is entitled to the maximum allowable workers compensation benefits under the Defense Base Act, a federal appeals court has ruled.

To reach its decision Thursday that the truck driver’s dry eye condition is compensable, the 2nd U.S. Circuit Court of Appeals in New York first had to determine if it had jurisdiction over Defense Base Act appeals....

...After reaching that conclusion, the court upheld decisions by an administrative law judge and a U.S. Labor Department benefits review board. They ordered the employer to compensate Jesse Barrios for a temporary total disability lasting from Dec. 20, 2005, through May 21, 2006, and a partial disability commencing on May 22, 2006.

The employer was also ordered to pay his medical bills.

Service Employees International appealed, arguing among other issues that Mr. Barrios suffered from an eye syndrome before he worked in Iraq and his condition was not caused by his employment there.

But the appeals court found that even a medical expert for the employer said there was “some possibility” that chronic dryness in Iraq could have worsened the eye problem.

Abstract: Makeup gets into your eyes

...and not only that, but maybe even more so when you're using eyedrops. And the moral of this story is...

Cosmetic Product Migration Onto the Ocular Surface: Exacerbation of Migration After Eyedrop Instillation.
Cornea. 2010 Feb 17. [Epub ahead of print]
Goto T, Zheng X, Gibbon L, Ohashi Y.
From the *Department of Ophthalmology, Takanoko Hospital, Matsuyama, Ehime, Japan; and daggerDepartment of Ophthalmology, Ehime University School of Medicine, Ehime, Japan.

PURPOSE:: Cosmetic product application may be an etiologic risk factor for dry eye syndrome. This study aimed to investigate whether a cosmetic product material (CPM) could migrate onto the ocular surface and whether eyedrop instillation might exacerbate this migration.

METHODS:: CPM was prepared by mixing equal volumes of hydroxyethyl cellulose gel (Scopisol; Senju Pharmaceutical Co. Ltd., Osaka, Japan) and a 10% fluorescein solution. Seventy-five female volunteers were randomly separated into three groups: the outer eyelash line group, in which CPM was applied on the upper and lower eyelids approximately 2 mm from the eyelash line; the eyelash line (EL) group, in which CPM was applied close to the eyelash line but without touching it; and the inner eyelash line group, in which CPM was applied on the eyelash line extending to the margin of the eyelids. The right eye was used for this study. At 5 and 30 minutes after CPM application, slit-lamp examination was carried out to detect fluorescence, an indication of CPM migration and contamination of the ocular surface. A strip of Schirmer test paper was used to collect tears, and the color of the paper was scored (contamination score: 0-5) to determine the relative quantity of CPM contamination on the ocular surface. In another set of experiments, 5 minutes after CPM application, one drop of balanced saline solution was instilled into the eye. Thirty seconds later, eyes were examined by slit-lamp microscopy and tears were collected to determine the migration percentage (eyes with CPM migration/total eyes) and contamination score.

RESULTS:: At 5 minutes after CPM application, the inner eyelash line group displayed a significantly higher migration percentage (96%) and average contamination score (3.35 +/- 0.77) compared with the outer eyelash line (12%; 0.15 +/- 0.34) and EL (20%; 0.35 +/- 0.32) groups. At 30 minutes, both the migration percentage and the average contamination score increased remarkably in the EL group (60% and 2.71 +/- 1.01). The migration percentage and average contamination score in the outer eyelash line group (P = 0.005 and P = 0.003, respectively) and EL group (P = 0.009 and P = 0.006, respectively) were significantly higher after eyedrop instillation compared with values before eyedrop instillation.

CONCLUSION:: CPM can migrate onto the ocular surface when applied close to the eyelid margin. This migration increases with time and can be exacerbated by eyedrop instillation.

Abstract: How many dry eye patients have lid wiper problems

Prevalence of Lid Wiper Epitheliopathy in Subjects With Dry Eye Signs and Symptoms.
Cornea. 2010 Feb 17. [Epub ahead of print]
Korb DR, Herman JP, Blackie CA, Scaffidi RC, Greiner JV, Exford JM, Finnemore VM.
From the *Korb Associates, Boston, MA; daggerPittsfield Eye Associates, Pittsfield, MA; double daggerTufts Medical School, Boston, MA; section signSchepens Eye Research Institute, Boston, MA; and parallelDepartment of Ophthalmology, Harvard Medical School, Boston, MA.

PURPOSE:: The purpose of this study was to investigate the prevalence of lid wiper epitheliopathy (LWE) in patients diagnosed with dry eye disease (DED).

METHODS:: Patients were recruited for two groups. Inclusion criteria for the DED group (n = 50) was: a score greater than 10 with the Standard Patient Evaluation of Eye Dryness questionnaire, fluorescein break-up time 5 seconds or less, corneal and conjunctival staining with fluorescein, lissamine green Grade 1 or greater (scale 0-3), and Schirmer test with anesthesia 5 mm or less. For the asymptomatic group (n = 50), inclusion criteria were: no dry eye symptoms, fluorescein break-up time 10 seconds or greater, no corneal or conjunctival staining, and Schirmer test 10 mm or greater. Sequential instillations (n = 2, 5 minutes apart) of a mixture of 2% fluorescein and 1% lissamine green solution were used to stain the lid wipers of all patients. LWE was graded (scale 0-3) using the horizontal lid length and the average sagittal lid widths of the stained wiper.

RESULTS:: In symptomatic patients, 88% had LWE, of which 22% was Grade 1, 46% Grade 2, and 20% Grade 3. In asymptomatic patients, 16% had LWE, of which 14% was Grade 1, 2% was Grade 2, and 0% Grade 3. The difference in prevalence of lid wiper staining between groups was significant (P < 0.0001).

CONCLUSIONS:: The prevalence of LWE was six times greater for the DED group and the prevalence of LWE Grade 2 or greater was 16 times greater for the DED group than for the control group. These data further establish LWE as a diagnostic sign of dry eye disease.

Abstract: Wavefront aberrations and lower tear meniscus

Simultaneous measurement of tear film dynamics using wavefront sensor and optical coherence tomography.
Invest Ophthalmol Vis Sci. 2010 Feb 17. [Epub ahead of print]
Koh S, Tung C, Aquavella J, Yadav R, Zavislan J, Yoon G.
University of Rochester Eye institute, Rochester, United States.

PURPOSE: To investigate tear film dynamics using simultaneous measurements of ocular aberrations and lower tear meniscus.

METHODS: Simultaneous measurements of wavefront aberration and lower tear meniscus were performed for 11 normal eyes and 7 eyes with short tear film break-up time dry eye (SBUT dry eye), which have tear film break-up time shorter than 5 seconds, using a wavefront sensor and an anterior segment optical coherence tomography (OCT). During the measurement, the subjects were instructed to blink every 6 seconds for a total of 30 seconds. From the measured aberration, root mean square (RMS) wavefront error and volume modulation transfer function (vMTF) induced by changes in tear film dynamics were calculated for a 5 mm pupil. Lower tear meniscus height (TMH) and area (TMA) were estimated from the cross sectional OCT images of lower tear meniscus.

RESULTS: There was a positive correlation between RMS and tear meniscus dimensions, and a negative correlation was found between the vMTF and tear meniscus in both groups. There was a moderate negative correlation between the post-blink initial RMS change and baseline TMH (R=-0.61) and TMA (R=-0.54) in SBUT dry eyes, which were stronger than in normal eyes. (R= -0.37, R= -0.38)

CONCLUSION: Tear meniscus dimensions increase with RMS over time, and tear quantity before the blink has a significant role in maintaining initial optical integrity, especially in SBUT dry eye. Simultaneous measurement of optical quality and tear meniscus has potential to improve our understanding of tear stability in normal and dry eyes.

Abstract: Tear meniscus changes after instilling artificial tear

Gosh. Artificial tears make things temporarily better... who woulda thunk.

Dynamic Changes in the Lower Tear Meniscus After Instillation of Artificial Tears.
Cornea. 2010 Feb 15. [Epub ahead of print]
Wang Y, Zhuang H, Xu J, Wang X, Jiang C, Sun X.
From the Department of Ophthalmology, Eye and ENT Hospital of Fudan University School of Medicine, Shanghai, China.

PURPOSE:: To compare the dynamic changes in lower tear meniscus area (TMA) and height after instillation of artificial tears in patients with dry eye and healthy controls.

METHODS:: Twenty-two eyes of 11 patients with dry eye and twenty eyes of 10 age- and sex-matched healthy subjects were included. The inferior tear meniscus height and area measurements were taken before and after instillation of 35 muL carboxymethyl cellulose (CMC) 0.5% and 1.0% (Allergan, Irvine, CA) on 2 consecutive days. The measurements were obtained before and 1, 5, 10, 15, and 30 minutes after instillation using anterior segment optical coherence tomography, RTVue-100 (RTVue, Optovue, Inc).

RESULTS:: The baseline lower TMA and height in the dry eye group were significantly lower than in the control group. A significant increase in TMA and height was found at 1 minute post instillation of 0.5% CMC in both groups, with findings returning to baseline levels at 5 and 10 minutes post instillation in the control group and dry eye group, respectively. The increase in TMA and height persisted for a longer time period in both groups with 1% CMC, versus 0.5% CMC. At 15 and 30 minutes, both tear meniscus parameters were still significantly higher in the control group and dry eye group, respectively.

CONCLUSIONS:: Artificial tears provide a significant yet temporary improvement in the tear meniscus. The anterior segment optical coherence tomography is valuable to measure dynamic changes in the tear meniscus

Abstract: 1-minute vs. 5-minute Schirmer

A Modified Schirmer Test in Dry Eye and Normal Subjects: Open Versus Closed Eye and 1-Minute Versus 5-Minute Tests.
Cornea. 2010 Feb 15. [Epub ahead of print]
Kashkouli MB, Pakdel F, Amani A, Asefi M, Aghai GH, Falavarjani KG.
From the Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

OBJECTIVE:: To assess the results of 1-minute and 5-minute Schirmer test (ST) when eyes are open (STo) and closed (STc) in normal subjects and patients with dry eye disease.

METHODS:: In a comparative, observational case series study, 34 normal volunteers (group 1) and 34 patients with dry eye disease (DED) associated with Sjogren syndrome (group 2) were included in the study. STo and STc for 1 minute and 5 minutes were performed separately for all subjects with an interval of at least 24 hours using Whatman No. 41 (5 x 60 mm) with bended end of the paper inserted into the lateral side of the lower conjunctival fornix.

RESULTS:: In group 1, there were 19 females and 15 males with a mean age of 20.8 years (range 18 to 23 years). In group 2, there were 29 females and 5 males with a mean age of 53.7 years (range 35 to 75 years). Mean value of STc was significantly less than STo in both 1 minute and 5 minutes in both groups. One-minute STo and STc showed significantly less wetting than the 5-minute test in both healthy and patients with DED. Normal distribution was observed for all the values. A significant correlation between 1-minute and 5-minute tests in both STo and STc were found in the two groups. Therefore, two equations were proposed to calculate the 5-minute from 1-minute ST in each group. Statistical analysis did not provide a reliable equation for calculating the standard ST (5-minute STo) from the most comfortable state (1-minute STc).

CONCLUSION:: Faster and more comfortable ST (1-minute) is a reliable test to calculate the 5-minute ST in both open and closed eyes, using the provided equations. The 1-minute STc is not a reliable test to calculate the 5-minute STo.

Abstract: Cytokines in dry-eyed tears

Analysis of inflammatory cytokines in the tears of dry eye patients.
Cornea. 2009 Oct;28(9):1023-7.
Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA.
Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York, USA.

PURPOSE: To determine the levels of 8 important cytokines and 1 chemokine in tears of patients with dry eye disease.

METHODS: Tear samples were collected from 7 patients with dry eye disease and 7 healthy volunteers, and impression cytology samples were collected from 3 of the dry eye patients and 3 of the normal controls. Tears were analyzed for the presence of 8 cytokines [interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-1 beta] and 1 chemokine (IL-8). The cytokines and chemokine in each tear sample were measured using Invitrogen's Multiplex Bead Immunoassays. The impression cytology samples were analyzed for IL-1 beta, IL-6, IL-8, and TNF-alpha mRNA expression using real-time reverse transcriptase polymerase chain reaction analysis.

RESULTS: All cytokines and the chemokine measured were significantly increased in the tears of dry eye patients as compared to normal controls. mRNA of all four markers was increased, and the fold increase correlated well with the fold increase of the cytokine concentration found in the tear samples.

CONCLUSION: Tears from dry eye patients contain significantly increased concentrations of cytokines that show correlation to severity of the disease. The upregulation of their respective genes in the conjunctiva suggests that the concentration increase is not the result of evaporative effects, but of overproduction. These findings suggest that cytokines may play an important role in dry eye disease and topical cytokine modulators may be explored as a therapeutic approach to dry eye disease.

Abstract: Studying age-related meibum changes

Physical Changes in Human Meibum with Age as Measured by Infrared Spectroscopy.
Ophthalmic Res. 2010 Feb 17;44(1):34-42. [Epub ahead of print]
Borchman D, Foulks GN, Yappert MC, Kakar S, Podoll N, Rychwalski P, Schwietz E
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Ky., USA.

Both lipids and mucins contribute to the stability of the tear film and lipids may inhibit tears from evaporating. Younger people have lower lipid viscosity, higher lipid volume, and a lower rate of tear evaporation. Since age-related changes in human meibum composition and conformation have never been investigated, as a basis for the study of lipid-associated changes with meibomian gland dysfunction, we used the power of infrared spectroscopy to characterize hydrocarbon chain conformation and packing in meibum from humans without dry eye symptoms in relation to age and sex. Meibum from normal human donors ranging in age from 3 to 88 years was studied. Meibum phase transitions were quantified by fitting them to a 4-parameter 2-state sigmoidal equation. Human meibum order and phase transition temperatures decrease with age and this trend may be attributed to lipid compositional changes. If meibum has the same thermodynamic properties on the surface of the tears as it does on the lid margin, a decrease in lipid-lipid interaction strength with increasing age could decrease the stability of tears since lipid-lipid interactions on the tear surface must be broken for the tear film to break up. This study also serves as a foundation to examine meibum conformational differences in meibum from people with meibomian gland dysfunction. Copyright © 2010 S. Karger AG, Basel.