Friday, September 30, 2011

Abstract: Acupuncture for dry eye, rabbit model

Interesting. I know plenty of people who have had acupuncture for dry eye, with mixed results. I have known some who found it very beneficial, though more often what I'm hearing is that people are finding it good for stress and perhaps improving coping with dry eye through the reduction of stress. If you're interested in this topic, check out acupuncture on DryEyeTalk. Here's an example of a recent discussion.

Efficacy of Acupuncture and Identification of Tear Protein Expression Changes Using iTRAQ Quantitative Proteomics in Rabbits.

To evaluate the effect of acupuncture on rabbit tear secretion and compare the difference in tear protein expression caused by acupuncture.

Materials and Methods:
Ten male New Zealand White rabbits were enrolled in this study. The following acupoints around the left eye, Extra 1 (Taiyang), BL 2 (Zanzhu) and SJ 23 (Sizhukong), were selected for acupuncture therapy. Each rabbit received 10 acupuncture sessions of 30 min, three times per week. A quantity of 50 μl rabbit tear was collected at the pre- and post-acupuncture stage in every subject, respectively. Total protein content analysis, one-dimensional gel electrophoresis and quantitative proteomics analysis (iTRAQ) were performed and the results were compared.

Generally, the tear protein expression after acupuncture was different from that before acupuncture though to some extent they were similar. The time spent collecting rabbit tear after acupuncture was shorter than that before acupuncture. The total protein content in rabbit tear pre- and post-acupuncture was 7.12 μg/μl versus 11.28 μg/μl, respectively. One-dimensional gel electrophoresis showed that tear proteins collected before acupuncture were substantially different than post-acupuncture proteins. In total, twenty-eight tear proteins were identified by iTRAQ. Associated with acupuncture were six up-regulated proteins (tear lipocalin, α-1-antiproteinase, histidine-rich glycoprotein, hemopexin, Vitamin D-binding protein, α-2-HS-glycoprotein) and five down-regulated proteins (Annexin A1, serum amyloid A-3 protein, Helicase-like transcription factor, 15 kDa protein A, protein S100-A9).

The rabbit tear protein expression difference caused by acupuncture indicates that acupuncture not only stimulates lacrimal gland secretion function but also induces the quantitative change of some proteins in rabbit tear, which may support a positive effect of acupuncture in the treatment of dry eye.

Curr Eye Res. 2011 Oct;36(10):886-94.
Qiu X, Gong L, Sun X, Guo J, Chodara AM.
Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University , Shanghai , China.

Abstract: Rasch analysis of OSDI

OSDI is definitely a less than perfect tool, but hey, it's the best we got (if I'm wrong please email me a link to something better) for the time being. We patients must have a scientifically validated way to quantify our symptoms or doctors simply won't take our pain seriously (especially in the absence of dramatic clinical signs). - This is also a big issue in getting drugs FDA approved - how can you prove improvement to both signs and symptoms if you can't quantify symptoms reliably?

Rasch Analysis of the Ocular Surface Disease Index (OSDI).

The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Its reliability and validity has been investigated within the classical test theory framework and, more recently, using Rasch analysis. The purpose of the present analysis was to more completely investigate the functioning of its response category structure, the validity of its three subscales, and the unidimensionality of the latent construct it is intended to assess.

Responses to the OSDI from 172 women participating in the Dry Eye in Postmenopause (DEiM) study who had previously been diagnosed with dry eye or reported significant ocular irritation and dryness were analyzed. Response category structure and item fit statistics were evaluated for assessment of model fit. Person separation statistics were used to examine the validity of the subscales. Unidimensionality was assessed by principle component analysis of model residuals.

Results:The recommended five-category response structure resulted in disordered response thresholds. A four category structure resulted in ordered thresholds. Item infit statistics were acceptable for all 12 items. Person separation with this category structure was adequate, with person separation index of 2.16. None of the three subscales demonstrated adequate person separation. PCA showed one other significant factor onto which the three environmental items loaded significantly.

Conclusions:All items demonstrated acceptable fit to the model after collapsing categories to order the response thresholds. The original subscales did not prove valid, and there is some evidence of multidimensionality and poor targeting.

Invest Ophthalmol Vis Sci. 2011 Sep 24. [Epub ahead of print]
Dougherty BE, Nichols JJ, Nichols KK.
The Ohio State University College of Optometry, Columbus, OH.

Abstract: Corneal neuropathic pain and blepharospasm

I really appreciate starting to see things in the pain journals on this topic.

Chronic (neuropathic) corneal pain and blepharospasm: Five case reports.

Pain and focal dystonias have been associated with chronic pain conditions such as complex regional pain syndrome. Corneal pain, frequently known as "dry eye", may be a neuropathic pain condition with abnormalities of the nerve plexus. Here we present 5 case histories of patients with defined corneal pain (with associated neuropathic features) and objective measures of changes in the nerve plexus and associated blepharospasm. A putative relationship between pain and blepharospasm suggests potential involvement of the basal ganglia in both these conditions.

Pain. 2011 Oct;152(10):2427-31. Epub 2011 Jul 12.
Borsook D, Rosenthal P.
Center for Pain and the Brain, McLean Hospital, Massachusetts General Hospital, and Children's Hospital of Boston, Harvard Medical School, Boston, MA, USA.

Wednesday, September 28, 2011

Abstract: Demodex

Clinical and immunological responses in ocular demodecosis.

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.

J Korean Med Sci. 2011 Sep;26(9):1231-7. Epub 2011 Sep 1.
Kim JH, Chun YS, Kim JC.
Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.

Tuesday, September 27, 2011

Opinion: Are some of us murdering our meibomian glands?

I have observed a trend over the past couple of years where for various reasons more people seem to be overdoing eyelid care in hopes of improving chronic MGD. They are applying heat packs twice or more each day; scrubbing and massaging their lids frequently; and attempting to express the glands regularly. I've even observed some of the savviest patients purchasing medical instruments intended for professionals and using them at home to express their glands.

As a longtime proponent of lid hygiene and heat treatment for MGD I have viewed this trend with increasing concern because I fear that inappropriate use, and over-use, of such treatments might delay rather than assist recovery of the meibomian glands. As I so often have over the years, I went to the doctor who first helped me understand dry eye diseases to elucidate this topic for me. What follows is an article that she wrote for DEZ readers in the wake of our discussion about whether some of us may be actually beating our meibomian glands to death. Enjoy, and please let us know what you think in comments here or via email/dryeyetalk/etc.

Expressing the meibomian glands
by Sandra M. Brown, MD - Cabarrus Eye Center, Concord NC

The meibomian glands live in the upper and lower eyelids. There are approximately 15 - 20 glands per lid. The gland openings lie on the edge of the eyelid just inside the eyelash line. The body of the gland is inside the tarsal plate, which is a very thin piece of cartilage that gives the eyelid its defined shape. When your doctor everts your lid (flips it inside out) he is flipping over the tarsal plate.

Although most diagrams of meibomian glands show a hollow tubular structure that looks like a permanently open space, a meibomian gland is more of a potential space. If the gland is empty of meibomian oils, it collapses in on itself. In fact even when the gland is "full" only a very thin film of oils may actually separate the cells lining the walls of the meibomian gland.

Meibomian oils are not squirted onto the surface of the eye. They seep out slowly under the gentle pumping action of eyelid blinking, combined with continuous oil production which pushes oils out onto the eye lid margin when the gland's potential space is fully expanded.

When the eyelid margin becomes inflamed, this inflammation can "cap off" the meibomian gland orifices. There are numerous causes of eyelid margin inflammation that will not be discussed here. If the glands continue to vigorously produce oils, the oils erupt through the sides of the glands and coalesce into a mass commonly referred to as a stye. However in many patients, obstruction of normal oil seepage causes the meibomian gland to decrease production and the oils retained in the gland become thick and degraded.

In the past 2 - 4 years, eye care providers have become more widely aware of the connection between meibomian gland dysfunction and ocular surface symptoms. One simple office test is to lightly press on the glands while the patient is seated at the slit lamp. The examiner is looking for the quantity and quality of oils, how many glands express, how hard s/he has to push to make this happen, and how readily the oils disperse into the tear film. Meibomian oils are quite easy to see at the slit lamp but essentially impossible to see with the naked eye except through elaborate magnification methods.

It is not necessary for 100% of the meibomian glands to function for adequate oils to be secreted into the tear film. Many asymptomatic patients have far fewer than 100% of the glands producing oils at any given time. Lower lid meibomian glands seem to "take a hit" sooner that upper lid glands, so it is important for your doctor to express both upper and lower lids to give your glands an overall function score. Patients with about 80% of their upper lid glands functioning well may have no symptoms even if the lower lid glands are producing almost nothing.

Eye care providers sometimes prescribe meibomian gland self-expression or patients take it upon themselves to "clear out" their glands periodically. Generally the process is to apply heat to liquefy the oils, followed by eyelash cleaning (or sometimes the reverse order) and then gland expression.

A note on hot compresses. The temperature of eyelid skin is slightly below core "body temperature" and meibomian oils become more liquid just a little above core body temperature. So moderate, sustained heat can keep viscous oils thinner. Patients who use very hot compresses that they can tolerate for only 1-2 minutes are going about it the wrong way. Washclothes are ridiculous due to the very rapid cool-down. There is no difference between dry and wet heat from the perspective of the interior of the meibomian gland. A compress that stays "definitely warm" witout being uncomfortable for at least 4 minutes is probably the most effective approach. It is impossible to really "study" the differences between compress methods.

As regards meibomian gland self-expression, there are several problems with this activity.

First, not all meibomian gland problems are due to blockage of the orifices. If the glands are simply under-producing oils (a common problem in peri-menopausal women) pushing on them won't do anything. If the lid margin inflammation is not under control and the orifices are tightly blocked, oils may not express even with hard pressure. So the treatment is not helpful. But secondly, self-expression can be harmful.

Remember that the gland is a potential space containing a small volume of oil. If you express all the oil out of the gland, you have probably expressed several days' worth of "production". You have depleted your supply. When the gland is empty, it collapses in on itself and the cells lining the potential space come into contact with each other without an intervening "oil slick". This allows the cells to adhere to each other. As the gland refills with oil the potential space expands and the cells separate. Repeated expression can lead to the cells permanently adhering, causing obstructions deeper in the gland. This process will be hastened by the microtrauma induced through the mechanical pressure, especially if applied vigorously and often.

I have seen patients who have basically murdered their meibomian glands through excessive self-expression. How do I know? Because the glands in the far nasal and temporal (ear side) areas are harder to reach. It is also more difficult to apply direct firm pressure to the glands in the upper lids than to those in the lower lids. So I see more non-functioning glands in the centers of both lids than the corners, and the lower lids have more non-functioning glands than the upper lids.

When is self-expression helpful? Some patients have mildly occluded orifices or tend to produce oils that don't seep well. They get into a "stagnation" situation. As part of their overall rehabilitation which MUST include efforts to improve oil quality and open the orifices, mild self-expression following a hot compress can be beneficial.

If you are a frequent (more than once per week) or aggressive self-expresser, ask yourself whether you are doing this "philosophically" because it seems like a smart thing to do or whether expressing truly improves your symptoms. If you are expressing several times per day, it is extraordinarily unlikely that you are getting a "useful" amount of oils onto the ocular surface each time. This habit will only increase the microtrauma to the meibomian gland structure.

Meibomian gland self-expression can be useful at certain stages of treatment. It is recommended by eye care providers, including those who specialize in ocular surface disease. It is important to understand that you can overdo it. You should not use self-expression unless instructed to do so by your eye care provider. If you have ocular surface pain and your provider has never expressed your glands, find a different doc.

What if you are a non-producer? Patients whose meibomian glands have ceased production are in a particularly difficult state. Peri- and post-menopausal women are most prone to this condition since meibomian gland function is regulated by androgen hormones. Some women become abruptly dry during pregnancy and don’t recover after pregnancy. Conversely some women have symptoms before pregnancy and actually feel better during pregnancy. We do not have a good understanding of the complex hormonal interplay that affects meibomian gland function. However, if your glands aren't making oils because they aren't receiving "go" signals from hormones or ocular surface nerves, many of the treatments described above will not be effective. Low production can combine with eyelid inflammation to further reduce the quality and quantity of oils reaching the tear film. Certainly related problems such as eyelid inflammation should be addressed. But for patients whose essential problem is markedly reduced production, it is particularly important to leave your meibomian glands alone!

Remember that the purpose of meibomian gland oils is to stabilize the tear film structure and slow evaporation. Barrier methods to slow evaporation (goggles, masks, etc.) are particularly helpful in this circumstance.

What helps meibomian glands and how:

heat - liquifies oils which tend to become more viscous just below body temperature (eyelid skin cooler than core body temp); see comments above about correct hot compress

doxycycline and minocycline, erythromycin - low dose for at least 60 days - acts as an anti-inflammatory which opens the orifices, thins out the oils in some fashion that we don't understand, decreases the bacterial load on the eye lid margins which opens the orifices

TobraDex ointment - anti-inflammatory, decreased bacterial load; intraocular pressure must be followed if used for more than 1 month

Restasis - in my experience anti-inflammatory effects can improve meibomian gland inflammation as well

omega oils - antiinflammatory, antioxidant, 'good ingredient' for oil production

Azasite applied to eye lid margins (topical equivalent of erythromycin) - antibacterial, maybe something else as well? seems to work for some people not others

Monday, September 26, 2011

Abstract: Ocular surface disease treatment algorithm

This is a nice summary of steps involved in treating dry eye.

A practical treatment algorithm for managing ocular surface and tear disorders.

Management of ocular surface irritation and morbidity associated with dry eye has been plagued by the complex interplay of different pathogenic elements and substantial variability of ocular surface deficits in patients. A practical algorithm is proposed to achieve effective management of dry eye. When the eye is open, ocular surface health is governed by a stable tear film that is maintained by neuroanatomic integration via 2 reflexes. Any dysfunctional element in this neuroanatomic integration is potentially pathogenic and creates ocular surface deficits leading to dry eye. In general practice, 5 major dysfunctional elements have been identified: decreased ocular surface sensitivity, aqueous tear deficiency, lipid tear deficiency, delayed tear clearance, and ineffective tear spread. Clinical workup should be individualized to identify all such dysfunctional elements in each patient through history taking, external and slit-lamp examination, and special tests. However, practical management lies in the detection of delayed tear clearance. The following strategies are advised: (1) eliminate all intrinsic inflammatory, infectious, allergic, and toxic insults, especially those associated with delayed tear clearance; (2) correct diseases that impede and interfere with tear spread and capacity; (3) create delayed tear clearance for aqueous tear-deficient dry eye by punctual occlusion; and (4) treat lipid-deficient dry eye after sufficient aqueous tears have been conserved. The aforementioned algorithm ameliorates ocular surface irritation and curtails morbidity in most patients. This algorithm can also be adopted for complex cicatricial ocular surface diseases before managing the remaining deficits resulting from hydrodynamic deficiency.

Cornea. 2011 Oct;30 Suppl 1:S8-S14.
Tseng SC.
From the Ocular Surface Center and Ocular Surface Research & Education Foundation, Miami, FL.

Drugs in development: VGX-100

Early stage research but sounds interesting.

VGX-100 Identified as Potential New Therapy for Dry Eye Disease

MELBOURNE, Australia, Sept. 13, 2011 /PRNewswire via COMTEX/ -- Data published in the scientific journal Archives of Ophthalmology generated by investigators at the Schepens Eye Research Institute led by Harvard University Professor Reza Dana.

VGX-100 significantly reduced inflammation and corneal epitheliopathy in a mouse model of Dry Eye Disease.

Data indicates major potential opportunity for VGX-100 as a therapeutic for Dry Eye Disease.

Circadian Technologies Limited (asx:CIR)(otcqx:CKDXY) announced today the publication of data in the scientific journal Archives of Ophthalmology showing that its lead development molecule VGX-100, a human antibody against the angiogenic and lymphangiogenic molecule VEGF-C, can significantly reduce inflammation and corneal tissue damage associated with Dry Eye Disease (DED). The data indicates a major new therapeutic opportunity for VGX-100 in the DED setting.

The manuscript entitled "Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease" Arch Opthamol. Dol:10.1001/archopthamol.2011.266 is accessible via the Archives of Ophthalmology website ( ).

DED is a complex, immune-mediated disorder of the ocular surface that has multiple causes and affects about 5 million Americans above the age of 50 years. It is estimated that 10% of Australians will suffer from the condition at some point in their lives. DED severely impacts the vision-related quality of life and the symptoms, including persistent dryness, burning, light sensitivity, pain and blurred vision, can be both psychologically and physically debilitating. The current therapeutic options for DED are limited and mostly palliative. Currently, topical cyclosporine-A is the only approved treatment for DED.

The study, which was led by Professor Reza Dana and Dr. Sunali Goyal of the Schepens Eye Research Institute, Harvard Medical School Department of Ophthalmology, showed that administration of VGX-100 was able to significantly reduce inflammation, lymphangiogenesis and corneal damage in a mouse model of DED.

Prof Reza Dana, MD MSc MPH. Claes Dohlman Chair in Ophthalmology, Professor of Ophthalmology, Harvard Medical School, Co-Director of Research at Schepens Eye Research Institute and senior author of the study said: "Dry Eye Disease is suffered by millions of people in the U.S., but current treatments have significant limitations, and effective treatments are not available for many patients. This current study builds on our previous findings demonstrating that VEGF-C, VEGF-D and VEGFR-3 are upregulated in DED corneas, and demonstrates for the first time that an anti-lymphatic effect, caused by the blockade of VEGF-C, has significant beneficial effects in treating the condition. We strongly believe that blocking lymphangiogenic molecules could become a major new paradigm for the treatment of DED."

Mr. Robert Klupacs, CEO of Circadian Technologies, said: "We have always believed that blockade of VEGF-C will have clinical utility in a variety of conditions, in addition to treating solid tumours. This very exciting data generated by our collaborators at Schepens offers significant opportunities for us to leverage our investment in the VGX-100 oncology program and undertake additional preclinical and clinical development activities for VGX-100 in DED, a disease which still remains extremely difficult to treat."

Support groups: Oct 6, Rochester NY, thyroid eye disease

Kudos to Patricia Marino for organizing this. Should be well worth attending... James Aquavella is a superb corneaMD and will be participating.

Flaum Eye Institute Expert to Discuss Thyroid Eye Disease Oct. 6
New support group forms for people with painful ophthalmic condition
A new support group for people with thyroid eye disease – a painful condition resulting from Graves’ disease – will meet at 5:30 p.m. Thursday, Oct. 6, at the Flaum Eye Institute at the University of Rochester Medical Center, 210 Crittenden Blvd. James Aquavella, M.D., cornea surgeon with the Eye Institute, will discuss dry eye related to the disorder and offer tips for relief.

Thyroid eye disease is closely associated with Graves' disease, an autoimmune disorder and the leading cause of hyperthyroidism, or overproduction of the thyroid gland. The eye problems occur when cells from the immune system attack the muscles and other tissue around the eyes, causing inflammation and a build-up of muscle tissue and fat behind the eye socket. As the deposits grow, it causes the eyeballs to bulge. It’s long believed that the late actor Marty Feldman, best known for his role in “Young Frankenstein,” had thyroid eye disease.

The Rochester-area support group is open to anyone with Graves’ disease or thyroid eye disease, as well as their family members. It offers a forum to share concerns, feelings and information, and offers peer support and encouragement to patients to help them cope with their illness. Spouses and caregivers also can gain a better understanding of the disease and how to support their loved ones. Advance registration is requested. Contact Steve Kofron at (585) 275-3977.

Patricia Marino, Ph.D., an organizer of the group, will share her story of diagnosis and treatment. The retired Rochester City Schools lead teacher and specialist/coach was diagnosed Graves’ disease in 2005. Under the care of Flaum Eye Institute Director Steven Feldon, M.D., M.B.A., an international expert in thyroid eye disease research and care, Marino has overcome most of her symptoms and related challenges. She hopes to offer others helpful support and advice as they cope with the illness.