Abstract: Dry eye in Jeddah, Saudi Arabia

I don't know what to make of this. I mean, I know it's dry there, but....

Or, is accompanying someone to the eye doctor a risk for dry eye in Jeddah?

Prevalence of dry eye in the normal population in Jeddah, Saudi Arabia.
Orbit. 2009;28(6):392-7.
Bukhari A, Ajlan R, Alsaggaf H.
Department of Ophthalmology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. amalbukhari@hotmail.com

PURPOSE: To estimate the prevalence of dry eye disease in the normal non-complaining population.

METHODS: Prospective systematic random sampling study of 251 subjects who accompanied patients with appointments to the eye clinic. Interviewers administered a dry eye symptoms and risk factor questionnaire. Tear film break up time, fluorescein corneal staining and Schirmer's test were performed. Slit lamp examination to evaluate the lid margins, Meibomian glands and ocular surface structures was also performed.

RESULTS: Dry eye was diagnosed in 234 (93.2%) subjects on the basis of presence of one or more symptoms occurring often or most of the time, together with one or more of the following signs: tear film break up time < or = 10 seconds, fluorescein corneal staining > or = grade 1 and Schirmer test score < or = 5 mm. There was no statistically significant association between dry eye with advancing age or gender. Blepharitis was detected in 215 (91.9%) of the dry eye cases. Smoking was found to be the second most common risk factor as 18.8% of the dry eye cases were smokers. Sicca syndrome was found in 24.4% of the subjects.

CONCLUSION: Dry eye is very prevalent disease. Blepharitis was found to be very common among dry eye cases. There was no statistically significant association between dry eye and age or gender in our study population

Abstract: Vesicare and dry eye side effects

I have really been appreciating that more trials of non-eye drugs have been evaluating and reporting dry eye side effects. Here's one for a drug for overactive bladder.

Effects of solifenacin on overactive bladder symptoms, symptom bother and other patient-reported outcomes: results from VIBRANT - a double-blind, placebo-controlled trial.
Int J Clin Pract. 2009 Dec;63(12):1702-14.
Vardy MD, Mitcheson HD, Samuels TA, Wegenke JD, Forero-Schwanhaeuser S, Marshall TS, He W.
Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, NY 10463, USA. dr.vardy@gmail.com

AIM: The aim of this study was to evaluate the efficacy of solifenacin on symptom bother using the Overactive Bladder Questionnaire (OAB-q).

METHODS: In VIBRANT, a double-blind, US-based trial, patients with OAB for > or = 3 months received flexibly dosed solifenacin or placebo for 12 weeks. At baseline and 4-week intervals, patients completed the OAB-q [symptom bother and health-related quality of life (HRQL) scales] and 3-day bladder diaries; other patient-reported outcome measures were also assessed at baseline and week 12. The primary efficacy end-point was the change from baseline to end of treatment (EOT) on the OAB-q Symptom Bother scale. Adverse events (AEs) were monitored.

RESULTS: At EOT, solifenacin (n = 377) vs. placebo (n = 374) significantly improved mean symptom bother (-29.9 vs. -20.4, p < 0.0001), HRQL total (25.3 vs. 16.7, p < 0.0001) and all HRQL domain scores (Ps < 0.0001). Solifenacin vs. placebo significantly improved daily episodes of urgency, incontinence and frequency but not nocturia. Significant separation from placebo was evident as early as week 4. Overall, significantly more solifenacin vs. placebo patients reported treatment benefit (84% vs. 63%), satisfaction (80% vs. 59%) and willingness to continue (79% vs. 60%; Ps< 0.0001). Treatment-related AEs in solifenacin vs. placebo patients were dry mouth (13% vs. 2%), constipation (8% vs. 2%) and dry eye (2% vs. 0.3%).

CONCLUSIONS: As early as week 4 and through EOT, flexibly dosed solifenacin significantly improved OAB symptom bother and HRQL as well as the symptoms of urgency, frequency and incontinence compared with placebo. Significantly more solifenacin patients reported treatment benefit and satisfaction at week 12 compared with placebo.

Abstract: Tear meniscus volume following punctal occlusion

More evidence in favor of plugs. Sort of. Collagen plugs increase tear meniscus if you're dry, don't if you're not; do not affect Schirmer score if you're dry, actually lower it if you're not dry. Hm.

Tear meniscus volume in dry eye following punctal occlusion.
Invest Ophthalmol Vis Sci. 2009 Nov 20. [Epub ahead of print]
Chen F, Shen M, Chen W, Wang J, Li M, Yuan Y, Lu F.
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, China.

Purpose: To use optical coherence tomography (OCT) to evaluate the effect of punctal occlusion on tear meniscus volume in dry eye patients.

Methods: Occlusion of both upper and lower puncta with collagen plugs was performed on one eye of 20 dry eye patients and 20 normal subjects. The upper and lower tear menisci were imaged simultaneously by real-time OCT before punctal occlusion and repeated on days 1, 4, 7 and 10 afterwards. The heights, cross-sectional areas, and volumes of the menisci were obtained. Schirmer I test with anesthesia and tear break-up time (TBUT) were also performed.

Results: At baseline, both upper and lower tear meniscus heights and volumes in dry eye patients were smaller than those in controls (P < 0.05). The lower tear meniscus volume was 0.28 +/- 0.09 mul in dry eye patients and 0.55 +/- 0.22 mul in controls at baseline (P<0.05). After punctal occlusion, the Schirmer I test scores of dry eye patients did not change (P>0.05), but the heights and volumes of both upper and lower tear menisci increased (P<0.05). In control subjects, Schirmer I test scores decreased (P<0.05), but heights and volumes of both upper and lower tear menisci did not change (P>0.05).

Conclusion: Punctal occlusion induced increases of both upper and lower tear meniscus volumes in dry eye patients. The absence of change in the tear menisci of control eyes may indicate the presence of an auto-regulatory mechanism in the tear system for maintaining a balance of tear volume.

Abstract: Smartplugs, canaliculitis & plug removal

Prevalence of canaliculitis requiring removal of SmartPlugs.
Ophthal Plast Reconstr Surg. 2009 Nov-Dec;25(6):437-9.
Prevalence of canaliculitis requiring removal of SmartPlugs.
Hill RH 3rd, Norton SW, Bersani TA.

PURPOSE: To report the first accurate prevalence of canaliculitis associated with the use of the SmartPlug.

METHODS: All patients from a single private ophthalmology practice who received SmartPlugs from 2002 to 2007 were identified. All patients from the private ophthalmology practice that developed canaliculitis secondary to SmartPlug insertion were referred to a single private ophthalmic plastic and reconstructive surgery office. A retrospective review of those 17 patients was performed.

RESULTS: From 2002 to 2007, a total of 235 patients were identified from a single private ophthalmology practice with a total of 402 SmartPlugs inserted. Of those 235 patients, 17 developed canaliculitis and were referred to a single private ophthalmic plastic and reconstructive surgery office. The prevalence of canaliculitis per patient was 7.23%. The prevalence of canaliculitis per SmartPlug inserted was 4.73%. The average time from SmartPlugs insertion to onset of symptoms was 3 years. All affected patients required canaliculotomy and plug removal.

CONCLUSIONS: This is the first study reporting the prevalence of canaliculitis associated with the use of the SmartPlug. All affected patients required surgical intervention, after which many continued to have dry eye and one required bilateral Jones tubes. Ophthalmologists using the SmartPlug for the treatment of dry eye syndrome should carefully weigh the risks and benefits of their use.

Moorfields' new dry eye site

UK users... Moorfields recently launched a new website dedicated to dry eye.

Dry Eyes Medical

Nothing spectacular as dry eye websites go, but all the same it's nice to see UK resources and attention to dry eye expanding. In treatments, it mentions moisture chambers and sclerals which most sites of similar superficiality don't.

Treating MGD early

There was an interesting 'panel' discussion on PCON recently about whether to treat lid margin disease (MGD) in patients who do not yet have symptoms (don't hurt). I'm posting some highlights here because I think this is a very timely topic. While I'm not sure I'm crazy about the idea of them prescribing all these drugs to people with a very mild case, on the other hand the fact that they are identifying the signs and educating their patients about it absolutely thrills me. That's surely a sign of significant progress. This is not, obviously, knowledge diffused evenly through optometric circles, else we would not still be hearing so frequently from people with raging lid margin disease who were not properly diagnosed, let alone treated, by their first four doctors. But progress leads to more progress.

Panel: Treating asymptomatic lid disease improves comfort, long-term results

We now understand the profound influence of adequate meibomian gland secretions on ocular comfort and quality of vision.
(Dr. William Townsend)

Define "we", please? :-)

Perhaps this could be rephrased as "We all ought to, and a growing number of us actually do now understand..."

We treat all patients with active meibomian gland dysfunction to prevent ongoing inflammation and tissue damage. Therapeutic modalities such as warm compresses, lid expression, systemic tetracyclines, oral omega-3 essential fatty acids and cyclosporine A have been shown to positively affect meibomian gland disease. While the immediate benefits of therapy such as increased gland output and visual enhancement are desirable, the real benefits of long-term therapy (preserving meibomian gland function and preventing atrophy) are the real effects that the patient will appreciate years later.

The management of lid disease is particularly challenging because although the provider may recommend appropriate treatment, the task of carrying out the administration of the various therapies falls on the patient. Early detection and treatment may save him or her from the discomfort and annoyance of advanced meibomian gland disease years later.
(Dr. William Townsend)

Currently, AzaSite, as well as Restasis, is an off-label treatment option for blepharitis and meibomianitis. However, with evidence growing that drugs such as these are proving beneficial and offering our patients an actual treatment vs. palliative care, I have begun prescribing treatment to previously asymptomatic patients. My “go to” treatment plan includes the standard warm compresses and lid hygiene (preferably with some type of commercial lid scrub) and AzaSite twice daily for 2 days and then once daily for the next few weeks. It is the treatment plan I put myself on.
(Dr. Blair Lonsberry)

When I treat asymptomatic patients with signs of blepharitis, I take the basic philosophical approach that no patient ever starts with severe lid margin disease. Most patients start with a mild case that, left untreated, progresses to more severe forms. That being said, I explain to patients with lid margin disease that an infection or inflammation of the lid margin left untreated can progress to significant symptoms that include itching, burning, chronic redness and uncomfortable contact lens wear and that it can also make other conditions such as dry eye worse. After a thorough explanation most patients decide to pursue treatment.
(Dr. Scot Morris)

Patients are not always as asymptomatic as they seem at first glance. Asymptomatic and completely satisfied are two different things. I ask patients about dryness, contact lens wearing time and red eyes. I always discuss my findings, as well as the risks of doing nothing and benefits of treatment.

Foaming eyelid cleansers, such as OcuSoft Lid Scrub Foaming Eyelid Cleanser (OcuSoft, Rosenberg, Texas) make it easy for patients to treat mild blepharitis in the shower. It is surprising how many asymptomatic patients return much happier, simply with a minimal routine change.
(Dr. Christine Sindt)

Heading to Boston at last

Aaaaaah. I have been trying to work in a trip to Boston Foundation for how many months now? Finally, finally it has worked out. Leaving Sunday, returning Wednesday with brand new eyeballs. Well, not quite that, but new prostheses (did you know sclerals are actually prosthetic devices?). Hurray, hurray.

MG Expressor Kit

...And in that same EyeWorld article, there was mention of a new kit for doctors to express those glands for the rest of us. Personally I don't see why a kit's needed (rice anyone? and fingers?) but hey, the more medical devices around for it the more doctors will, hopefully, be learning about the need to be conversant in meibomian gland manipulation. WAKE UP, DOCTORS. The population is aging. MGD is booming. Patients are shopping around for doctors on the basis of how meibomianitis literate they are. Are you? And by the way, stock analysts care about dry eye. Do you? Well, OK, if you're reading this blog you probably do. Maybe you could forward a link to a colleague who doesn't... yet.

For less severe cases of meibomian gland dysfunction, Mario Gutierrez, OD, FAAO, has developed the MG Expressor Kit (Gulden Ophthalmics), which combines the traditional therapies of warm compresses and massage, though in a more rigorous form. The kit includes a gel mask that can be warmed, the expressor tool and sanitary caps that can be placed over the roller. Dr. Gutierrez described the technique.

“Once the lids are warm, it liquefies the contents of the meibomian glands,” he told PCON. “Then, we basically roll the tool on the eyelid near the eyelid margin, and that helps express the liquefied meibomian gland content.

“I typically warm up the eyelids, use the roller, really work the nasal eyelids — the glands — a little bit more,” he continued. “This seems to help the patient become less symptomatic if we can get the nasal meibomian glands working well. Then I’ll go back and warm the lids a little bit more, maybe for a minute or two more, and then go back and roll it one more time to try and liberate as much of the expressions as possible.”

According to Daniel Adams, OD, the expressor is best used at a horizontal angle, working from the lash line upwards.

“The gel pack should only be used for 3 minutes to warm the glands, and then the expressor tool should be rolled horizontally — not vertically — over the eyelid, forcing the meibum upwards,” Dr. Adams said in an interview. “You want to soften the oil that’s congealed in the gland, and once you are able to get it to a ‘soft butter’ stage, roll the glands and try to express it out.”

Maskin probe

Noticed all the buzz lately about the new Maskin probe?

EyeWorld discussed it in a recent article about "aggressive" (i.e. beyond doxy, azasite and classic compress/scrub routines) treatments for meibomian gland dysfunction.

The Maskin Meibomian Gland Intraductal Probe (Rhein Medical), developed by Steven L. Maskin, MD, helps remove obstructions within the duct. Dr. Maskin told Primary Care Optometry News that clinicians can enter the meibomian gland with the probe and provide “dramatic and immediate” relief to patients.

Blockages within the gland may be caused by fibrovascular tissue that grows into the duct with new blood vessel formation as well as an abnormal hyperplastic keratinized ductal epithelium or scarring in or over the orifice, he said.

“What I found when I entered the meibomian gland was that there was frequently some resistance deeper inside, within the duct, which was able to be relieved with mild pressure,” Dr. Maskin said. “When you apply that pressure, you’ll be able to penetrate through that and there will be a ‘pop’ characteristic of a fibrovascular membrane. You can create a patent open duct from orifice to the deeper duct. Patients’ lid tenderness dramatically and immediately improves.”

...But wait, lest you interpret my "beyond doxy, azasite, etc", bear in mind that it's probably in addition, not instead of:

...Marguerite McDonald, MD, shared her protocol with PCON. She first holds lidocaine gel against the lid margin to anesthetize the area where the probe will be inserted. Afterward, she prescribes a combination of topical and sometimes oral medications to treat the disease.

“For patients with moderate to severe meibomian gland disease, I place them on ‘soaks and scrubs’ twice daily, as well as on AzaSite (azithromycin 1%, Inspire), one drop in both eyes twice daily for 2 days followed by one drop daily for at least a month,” she said. “Some severe patients stay on AzaSite indefinitely.

“I ask the patients to rub the drop into the base of their lashes for a few seconds while their lids are gently closed, immediately after instilling the drop,” she continued. “In addition, many patients are placed on oral doxycycline (100 mg) twice daily for a week to 10 days, then 20 mg once daily for a few months, if not indefinitely.”

And of course, on DryEyeTalk it's been a subject of discussion for some months past, as in this thread.

Dropless ad

Have you seen the Lacrisert "Dropless" ad?

I can't post it because their site doesn't let you pinch its pix, but it's a shot of a comely and presumably 50yo+ lady with the photo cut off just below her shapely, bare shoulders. The text says "Freedom to go dropless."

In the staid world of ophthalmic pharmaceutical advertising where edgy means snapping a photo of the bottle from a new and different angle and progressive Restasis commercials are showing up on websites like commercialsihate.com, I thought it was pretty cute.

Abstract: The life and times of... normal meibomian glands

The Diurnal Secretory Characteristics of Individual Meibomian Glands.
Cornea. 2009 Nov 11.[Epub ahead of print]
Blackie CA, Korb DR.
From the *Korb Associates, Boston, MA; and daggerTearScience, Inc, Morrisville, NC.

PURPOSE:: To investigate the diurnal secretory characteristics of individual meibomian glands (MGs).

METHODS:: Ten subjects (4 females and 6 males) with healthy eyelid appearance and without dry eye symptoms were recruited (mean age = 23.8 +/- 1.8 years). Both right and left lower eyelids were marked in 3 places to locate 5 consecutive MGs in each third (temporal, central, and nasal) of the lower eyelid. A total of 15 MGs per eye were diagnostically expressed for 10 seconds on both right and left lower eyelids every 3 hours for 4 consecutive measurements over a 9-hour period.

RESULTS:: Thirty-four percent of all tested MGs yielded liquid secretion at all measurements. Sixty-nine percent of the tested nasal MGs yielded liquid secretion at all measurements in contrast to 31% of the central MGs and only 22% of the temporal MGs. The mean numbers of MGs secreting liquid oil were significantly higher in the nasal section relative to the central and temporal sections at all measurements (p < 0.001, all measurements).

CONCLUSIONS:: (1) A single MG is capable of secreting oil on demand over the course of a working day ( approximately 9 hours); (2) nasal MGs were the most likely to secrete upon demand over the course of day compared with the temporal and to a lesser degree the central MGs; and (3) secretory characteristics of individual MGs examined as a function of their location in the lower eyelid does not change diurnally.

Abstract: KLAL in LSCD

Long-term outcomes of keratolimbal allograft for total limbal stem cell deficiency using combined immunosuppressive agents and correction of ocular surface deficits.
Arch Ophthalmol. 2009 Nov;127(11):1428-34.
Liang L, Sheha H, Tseng SC.

OBJECTIVE: To determine the long-term outcomes of keratolimbal allograft (KLAL).

METHODS: Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP.

RESULTS: More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 microg/mL (SD, 0.6 microg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period.

CONCLUSION: Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Abstract: Topical naltrexone

Not all that relevant to our crowd (most of us would rather have a decrease rather than increase in corneal sensitivity!) but interesting nonetheless.

Dry eye reversal and corneal sensation restoration with topical naltrexone in diabetes mellitus.
Arch Ophthalmol. 2009 Nov;127(11):1468-73.
Zagon IS, Klocek MS, Sassani JW, McLaughlin PJ.

OBJECTIVE: To determine if topical application of naltrexone hydrochloride (NTX), an opioid antagonist, restores tear production and corneal sensation in rats with diabetes mellitus.

METHODS: Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10(-5)M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only.

RESULTS: Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle.

CONCLUSION: Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats.

CLINICAL RELEVANCE: Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.

Abstract: Stem cell transplantation

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye.
Bone Marrow Transplant. 2009 Nov 9.
Wang Y, Ogawa Y, Dogru M, Tatematsu Y, Uchino M, Kamoi M, Okada N, Okamoto S, Tsubota K.
[1] Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan [2] Department of Ophthalmology, The Eye and ENT Hospital of Fudan University School of Medicine, Shanghai, China.

We evaluated ocular surface alterations in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with or without chronic GVHD-related dry eye in a prospective study. Fifty eyes of 25 post-HSCT patients and 28 eyes of 14 age-matched healthy controls were included. Meibomian gland (MG) obstruction, tear evaporation rate, corneal sensitivity (CS), Schirmer test-I, tear break-up time (BUT) and ocular surface vital staining were examined. Conjunctival impression and brush cytology specimens were collected to evaluate the goblet cell density (GCD) and the inflammatory cell numbers. Obvious MG obstruction, decreased CS and enhanced tear evaporation rate were found in post-HSCT patients compared with normal controls. In addition, decreased conjunctival GCD, increased conjunctival squamous metaplasia and inflammatory cells were noted in cGVHD-related dry eyes compared with normal controls and post-HSCT without dry eye subjects. Furthermore, the conjunctival inflammatory cells were significantly higher in severe dry eyes compared with mild dry eyes (P=0.03). We found comprehensive ocular surface alteration in post-HSCT patients, regardless of whether they had cGVHD-related dry eye or not. The results suggest that the extent of inflammatory process seems to have a pivotal role in the outcome of the cGVHD-related dry eye.

Abstract: Aussie study on McMonnies questionnaire

McMonnies Questionnaire: Enhancing screening for Dry Eye Syndromes using Rasch Analysis.
Invest Ophthalmol Vis Sci. 2009 Nov 5.
Gothwal VK, Pesudovs K, Wright T, McMonnies C.
NH&MRC Centre for Clinical Eye Research, Department of Ophthalmology, Flinders Medical Centre and Flinders University of South Australia, Adelaide, Australia.

PURPOSE: To determine, using Rasch analysis, if the McMonnies questionnaire satisfied the properties of a measure and whether screening for dry eye syndromes (DES) could be enhanced using different scoring approaches.

METHODS: The questionnaire was self-administered by 43 female Sjögren syndrome patients (>45 years) recruited from a specialized rheumatology clinic and 140 age-matched controls. Data were scaled using Rasch analysis and assessed for response category behavior and ability to reliably discriminate between severity of participant's dry eye symptoms (i.e. person separation reliability; minimum acceptable value 0.80). Standard summary statistics of screening performance were calculated for raw and Rasch-scaled scores from Receiver-Operating Characteristic analysis including area under the curve (AUC). Best predictors (i.e. questions) from a discriminant analysis were used to calculate a discriminant function for both Rasch-scaled and raw scores.

RESULTS: Response categories were not used as intended, necessitating collapse of categories. Person separation reliability was inadequate (0.75). Rasch-scaled discriminant cut-off score of -2.29 logits from 7 items provided an AUC of 0.99 with 95% sensitivity. However, discriminant raw score from modification in the scoring of a question, i.e. use of medications (used singly rather than individual questions) provided AUC (0.97) not significantly different (z = 1.11, p = 0.27) with 98% sensitivity and required only 2 questions.

CONCLUSIONS: In this population, the McMonnies questionnaire does not function as a measure. However, various scoring methods can be used to efficiently screen for DES.