Am I missing possible treatments?

[cristiandryeyes]

indrep, What do you think of this new eye drop?

Aquoral facts:
Hyaluronic acid 0.4%
sodium phosphate monobasic monohydrate
dibasic sodium phosphate dodecahydrate
sodium chloride
water


Apparently it doesn't cointain Glycerin. But looking at the facts, Do you think it might be a good eye drop capable of changing osmolarity ?

I was looking for some alternatives to Oasis Plus since it's way too expensive for me.

If I need 14 drops or more /day and each Oasis plus box contains 30 vials that would mean that I need to buy 4 boxes/week (15 boxes/month) = 330 dollars/month.

[indrep]

christian, what drop are you currently using 14 times a day? My experience is people need about half the number of applications of TEARS PLUS than they do from other Preservative free drops. And around 90-120 days the number of PLUS applications needed lowers.

Each vial has about 6-8 drops in it.

The drop you describe looks good from an ingredient standpoint. The .4% HA concentration is high enough to induce molecular crowding(the sponge like matrix) however if the molecular weight of the HA is below 500,000 daltons it will not have the second component needed for molecular crowding.

Unfortunately you may not be able to find that out. Typically the HA drops in Europe and Japan I have researched have low molecular weight and try to make it up with higher concentrations.

[ringo]

Thanks to indrep and ringo for sharing your deep knowledge on this disease. I have read all your posts and I have reached a conclusion: THERE IS NO HOPE. Both of you have exhaustively tried to explain the underlying mechanisms of this disease, changes on the ocular surface and the role of inflammation and the inflammatory cascade BUT spent little time on the treatment matter which is in the end what we really CARE.


ringo's explanation seems a lot more convincing and REALISTIC to me BUT you leave little room for hope!. Actually I'd rather not have read some of your posts when you get too technical and everything makes so much sense and everything relates to my condition...because then, THEN IS WHEN I KNOW I'M IN TROUBLE.

On the other hand, indrep had a point until he talked about his wife as an example. Man, with all my due respect, artificial tears and warm compresses alone are not gonna cure us. AND I'm not waiting 2 years or more to check if you were right or not. When you've been doing warm compresses for THAT LONG, that's when you've to start thinking about the possible secondary effects of it.

Since you mentioned your wife's case, allow me to briefly tell you mine. Since I've been doing warm compresses, I've noticed MORE AND MORE RED VEINS AND INCREASED DRYNESS SENSATION DURING THE ENTIRE DAY. Of course, I have stopped them, but my eyes never got back to their initial state. I've never got any really relief from warm compresses, not even temporary relief.

So, All in all, I don't if it is good to know the details or simply ignore them. If you know the details you also know exactly how many possibilities you have to get over this. Where I am right now, I cannot assume I'm going to spend the rest of my life in this condition. So, if I'm going to stay like this, I need someone to tell me so I can take a decision whether I shall continue or not.

Dear Chris,
Dear Indrep,

I will try to correlate my posts with Indrep's as they seem to diverge in two opposite directons, which is not the case at all. Actually, the information provided inor posts complements each other, and thus also provides a comprehensive approach to treatment which addresses the mechanisms of the disease that both my posts, and those of indrep describe.

These mechanisms are correlated, and their treatments too, an not at all mutually exclusive, as it may look from the way the discussion here developed.

First, I hope I have understood Indrep point well: he talks about how in keratoconjunctivitis sicca decreased lacrimal gland secretion initiates ocular surface disease through a secondary increase in tear film osmolarity. Tear film osmolarity increases through a variety of mechanisms. Therapies that lower tear film osmolarity decrease the clinical signs of ocular surface disease and improve patient comfort.
Literature has demonstrated the role of osmolarity in tear homeostasis and disease pathogenesis.Elevated tear osmolarity has been identified as a global characteristic of dry eye disease. An increase in tear osmolarity results from a more concentrated salt concentration in tears, which occurs in both aqueous tear deficiency and evaporative dry eye, such as is seen in meibomian gland dysfunction.

Scientists had argued whether increased tear film osmolarity caused the ocular surface inflammation in dry eye, or whether the ocular surface inflammation caused the increased tear film osmolarity.However, in both cases, it is clear that something triggers the decrease in volume and quality of tears, before any osmolarity or inflammation related to it occurs.

This something that triggers the tear quantity/quality deficiency I have described in my previous posts in this same thread.

I do not contest the view that tear osmolarity is a major factor in the eye inflammation,and that by addressing it (decresing tear evaporation, the right artificial tears, punctal occlusion, goggles, etc.), the situation is improved; my point is that it is accompanied/preceded/and followed by many other factors contributing the the vicious cycle of never-ending inflammation on the eye; and these other factors should be addressed as well with proper treatments.

Dry eye is a complex multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Instability of the tear film may also cause an increased osmolarity of the tear film, thus triggering epithelial osmotic lesions and inflammation. The occurrence of such changes on the eye surface results in disturbances of homeostatic neurophysiologic mechanisms which further worsen the process and vicious pathophysiological cycles occur.

patients’ tears must be adequate both in quantity and quality. To maintain a healthy ocular surface, patients need enough tears to coat the eye, but tears must also have the proper chemical composition in order to nourish and protect ocular surface cells.

In fact, because hyperosmolarity can result from either a decrease in tear secretion or an increase in tear evaporation—the two pathways that produce ocular dryness—hyperosmolarity is believed to be a feature common to all cases of dry eye.However, it is not the reason for having tear defciency in the first place;nor is it the only factor participating in eye inflammation, especially when the neurophysiologic mechanisms controlling and monitoring the immune homeostasis of the eye get involved.

In addition,I agree with Indrep that hyperosmolarity causes ocular surface cell damage, which can be visualized by ocular surface staining. This damage occurs because ocular surface cell membranes are permeable; when they are exposed to hyperosmotic tears, water flows out of the cells in an attempt to balance the osmolarity of the intracellular fluid with the osmolarity of the surrounding tears. When this happens, ocular surface cells can become dehydrated, which damages cell membranes and changes the way proteins protect the ocular surface.

What Indrep is referring to, are studies like the following: in the September 2008 American Journal of Ophthalmology, Dr. Lemp states: “Tear osmolarity is considered a "central mechanism causing ocular surface inflammation, damage and symptoms, and the initiation of compensatory events in dry eye’.”
Dr. Lemp continues:
“Although the exact place of inflammation in the stream of events leading to ocular surface distress is not clear, its role is unmistakable.” He goes on to say, “In the use of cyclosporine to modulate immune activity and to suppress inflammation in dry eye, there is increasing evidence that the use of topical corticosteroids as temporary or pulsed therapy can be useful in reducing the damaging effect of inflammation.”(2) Here you can see tear 0smolarity being addressed by anti-inflammatory therapy as well, besides symptomatic treaments like tears and lmiting evaporation.
Furthermore, in recognition of the need to address inflammation, in addition to tear film osmolarity, the Report of the International Dry Eye WorkShop (DEWS), published in 2007,that Indrep constantly refers to, clearly established that “corticosteroids are an effective anti-inflammatory therapy in dry eye disease.”(3), and I quote:
2.2. Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol. 2008 Sep;146(3):350-356. Epub 2008 Jul 2. Review.
3. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):171.

When pathologists talk about idiopathic dry eye inflammation, they do not mean immune system on the attack and presence of swollen, red eyes. They mean an erratic failure in the function of antigen-presenting cells in their recognition of antigens and proteins secreted by epithelial cells of the conjuctiva,which is followed by the employment of effector lymphocytes on the ocular surface and a myriad of subsequent responses by other cells and enzymes, which is called a cascade of processes resulting in the development of an inflammatory state and disruption of the maintenance of local immunohomeostasis, eventually leading to tissue damage to the ocular surface. Tear osmolarity is a major feature of these subsequent changes.We have similar cascades taking place in allergic conjuctivitis.

In non-idiopathic dry eye, caused by systmic dsease like sjogrens, or roscea, the disease is caused by infiltration of teh glands of T-lymphocytes due to erratic function and regulation of these immune cells themselves, which in some cases can develp to lymphoma (total mutation and erratic proliferation of these lymphocytes). So, in this case tear deficiency is caused by the inflammatory cells themselves directly.

All this eventually leads not so much to the destruction of the tear glands, as to their neural isolation, due to inflammatory substances disrupting neural signalling pathways, damaging corneal nerves, etc. In surgery induced dry eye, the nerve damage is the initial factor for tear deficiency, and subsequent tear osmolarity and inflammation.

My point is we cannot improve overall, or prevent the progression of the disease by targeting tear osmolarity alone, or only with symptomatic measures.
I wish we could. But this is a multfactorial disease and treatmet should be comprehenisve, including Indrep's recommendations for treatment and anti-inflammatory and tear-stimulating therapy.(by the way, as i have said before cyclosporine is a tear glad srimulant, so-called lacrimostimulant, besides being antiinflammatory, as Indrep mentions it only as antiinflammatory).

Sorry for this long post, but I just felt the need to elaborate, so we can compbine or posts- me and Indrep, towards a common understanding and a common truth, not towards a useless debate o whether the chicken or the egg came first.

[indrep]

Ringo,
I'm glad you read the DEWS report. Here are a couple more that are educational in what helps treat dry eye disease:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1771021/
http://bjo.bmj.com/content/88/6/821.abstract

As with all disease there is no single approach that helps 100% of patients.

After reading these you will see that indeed perhaps a single cost effective product can be very useful in providing patient comfort, cell healing, reduction in inflammation, etc.

Also I will respectfully disagree on what comes first the chicken or egg. Once I know the egg becomes a chicken I can stop the process of creating more chickens.

Finding the cause is always important in finding ways to cure an issue.

[ringo]

Thank you for the links Indrep, and if you go back up to my post you will see i did not mean debating about the egg and chicken as debating about the cause of dry eye-- i just call any debate that goes astray and leads to no useful conclusions-- a debate about what came first, the egg or the chicken.

All I want to say is that I am glad our correspondene has been so productive, and did not end up as a useless debate

Thanks again,
Dani