Friday, November 23, 2007

Study: Gel-to-drop, for Rx or OTC

Hm. Is this basically a souped-up version of the Lacriserts concept, or more? Sounds interesting anyway.

It seems as though there are always some kind of technologies in the works to reduce or eliminate the need for eyedrop application. Several I've read about or been talked at about by excited inventors in the past year or so include a punctal plug that secretes drops, contact lenses used to deliver drugs, special glasses with a microchip and tiny jets aiming a stream of tiny drops at the eyes, and now this gel-to-drop drug delivery system. It will be interesting to see if any of these types of things ever really comes to fruition.

Sustained Ocular Drug Delivery from a Temperature and pH Triggered Novel In Situ Gel System.
Gupta H, Jain S, Mathur R, Mishra P, Mishra AK, Velpandian T.
Drug Deliv. 2007 Nov;14(8):507-15.

Various ocular diseases like glaucoma, conjunctivitis, and dry eye syndrome require frequent drug administration. Poor ocular bioavailability of drugs (< 1%) from conventional eye drops is due mainly to the precorneal loss factors that include rapid tear turnover, nonproductive absorption, transient residence time in the cul-de-sac, and the relative impermeability of the drugs to corneal epithelial membrane. These problems may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. Our present work describes the formulation and evaluation of an ocular delivery system of timolol maleate based on the concept of both temperature and pH-triggered in situ gelation. Pluronic F-127 (a thermosensitive polymer) in combination with chitosan (pH-sensitive polymer also acts as permeation enhancer) was used as gelling agent. The developed formulation was characterized for various in vitro parameters e.g., clarity, gelation temperature and pH, isotonicity, sterility, rheological behavior, drug release profile, transcorneal permeation profile, and ocular irritation. Developed formulation was clear, isotonic solution, that converted into gel at temperatures above 35 degrees C and pH 6.9-7.0. A significant higher drug transport across corneal membrane and increased ocular retention time was observed using the developed formulation. The developed system is a viable alternative to conventional eye drops for the treatment of glaucoma and various other ocular diseases.

Study: Where da numbers?

Right on boys. The acid test: IS LIFE BETTER with this drug? Let's see some numbers please. It's not new anymore - it's been around long enough to figure this out.

Pharmacoeconomics of new medications for common chronic ophthalmic diseases
Hirsch JD, Morello C, Singh R, Robbins SL.
Surv Ophthalmol. 2007 Nov-Dec;52(6):618-33

There is increasing pressure for medical care reimbursement to be linked to outcomes. New medications approved for glaucoma, age-related macular degeneration (AMD), and dry eye disease may offer improved outcomes, but they have higher acquisition costs. This article reviews published pharmacoeconomic studies assessing the incremental change in outcomes achieved vs. the increased medication costs incurred....Notably missing in all analyses are the effects of improved treatment on patient productivity. Although the diversity and small number of studies limit conclusions, there is some evidence that the newer glaucoma medications, as a group, produce economic offsets such as reduced glaucoma surgeries and fewer physician visits. Photodynamic therapy for AMD may be cost-effective when used early in patients with better visual acuity allowing cost-offsets over longer periods of time to be considered. The single pharmacoeconomic analysis of topical cyclosporine for dry eye disease was only hypothesis-generating. Comprehensive studies that investigate clinical, economic, and humanistic outcomes for the patient and society are needed to adequately assess the comparative value of current and future ophthalmic medications.

Study: "Osmoprotection"

Sorry but... my tolerance for hyperosmotalk wore out somewhere in the years of "complete dry eye relief for everyone" marketing which so far as I can tell has not yet completely relieved everyone.

Osmoprotection as a new therapeutic principle
Messmer EM, Ophthalmologe. 2007 Nov;104(11):987-990.

Dry eye syndrome is one of the most common disorders encountered in daily ophthalmological practice. New pathophysiological concepts have been developed over the last few years. Hyperosmolarity of the tear film is one of the key pathogenetic factors in the development of a - commonly subclinical - inflammation of the ocular surface, the lacrimal gland and the tear film in dry eye syndrome. Osmoprotective agents act through compatible solutes to prevent - at least in theory -a hyperosmolar tear film from damaging the ocular surface.

Monday, November 19, 2007

Another update on my BSLs (one more entry on a very long list for Thanksgiving this year....)

Well, last Monday I think I pretty much gave my BSLs the acid test, and they passed with flying colors.

First, I stayed up past midnight on Sunday. Had to take out my lenses around 10pm, so my eyes had two whole hours during which to dry out nicely before bed.

Next, I got up at quarter to three, showered, finished packing, and drove 1.5 hours through a wet windstorm to make an early flight. Managed to time the drive just right... on Monday mornings, if you don't make it to SeaTac at just the right time, you're screwed. I'm glad I took the time to print out my boarding pass, and wasn't checking luggage. Even so, within 5 minutes of my joining the 100+ line at security, it had doubled - at least.

Next, 2.5 hour flight to Orange County. Took out my lenses so I could doze.

Later, a 1-hour drive up towards UCLA in an air conditioned rental.

After dinner (i.e. long after sunset), a hasty drive to LAX.

Next, hanging out in another lovely dry fluorescent-lit airport waiting for a delayed inbound aircraft. Then, another 2.5-hour flight, arrival late at night, and last, I drove myself home in the middle of the night, arriving about 24 hours after I'd gotten up.

NOW, all that sounds just like business as usual to any normal business traveler. By my own travel standards of years ago, that's a light day. But for the past 6 years - in wintertime, at least - THIS IS A BIG DEAL for me. I could not have driven myself to the airport at 4 in the morning with or without rain and wind and debris, I could not have driven down a 10 lane LA freeway (that's an awful lot of starburst-and-halo-generating headlights and taillights) freeway after dark, and I most certainly could not have driven myself home in the middle of the night under any circumstances, let alone after spending an entire day in some kind of rigid contact lens.

With my current pair of T6 BSLs, I can do all that. It's amazing, and I am so grateful. Thank you Dr. Rosenthal, and Mark. :-)

Travel tip for road warriors:

I discovered on this trip that Ocusoft lidscrub foam 50mLs are exempt from the liquids restrictions BUT they trigger a search and an interesting conversation with the security folks, so, um, next time if I'm not checking luggage I'll leave them at home....

Newsblurb: Dry as a desert

Nothing special about the news item per se but there's kind of a cute photo of some fake eyeballs in the sand. (Wee bit of time on our hands today, have we???)

Ozarks Health
Dry As A Desert

The women's health group released a report this summer naming office jobs, many requiring prolonged computer use, as the work most likely to contribute to dry eye. Next are construction and manufacturing jobs, which expose workers to dust, allergens and wind.

Contact-lens users are especially vulnerable to dry eye, Esposito says, because the lenses draw moisture off the eyes.

The condition is more common in Hispanic and Asian women and in people with autoimmune diseases such as Sjogren's syndrome, lupus and rheumatoid arthritis. People who take antihistamines, diuretics, antidepressants and other medications are at higher risk, too.

Study: Meibum lipids, tear lipids...

...Something tells me this study is interesting, I just don't know why... If anyone wants to enlighten me, feel free!

Temperature-induced conformational changes in human tearlipids hydrocarbon chains.
Biopolymers. 2007 Oct 5-15;87(2-3):124-33.Click here to read Links
Borchman D, Foulks GN, Yappert MC, Ho DV.

As a first step to characterize human meibum and tear lipids, infrared spectroscopy was applied to characterize the molecular structure/conformation and packing of hydrocarbon chains. Temperature-induced phase transitions were fit to a sigmoid equation and were experimentally reproducible and were similar for multiple samples collected from the same person. No hysteresis was observed. Hydration of polar tear lipids increased their phase transition cooperativity, enthalpy and entropy. Hydrophobic interactions in meibum lipid (ML) were stronger than in tear-fluid lipids (TL), as reflected by the higher entropy and enthalpy of the gel to liquid crystalline phase transition of ML. The results of this study provide further evidence of the differences in the composition and structure of ML and TL. The conformational changes observed in the hydrocarbon chains of ML with temperature suggest that the observed therapeutic increased delivery of ML with eye lid heating could be related to the increased disorder in the packing of the hydrocarbon tails. This work also highlights the power of infrared spectroscopy to characterize molecular structure/conformation, and packing of human tear lipids and provides a basis for future studies of tear film lipid composition-structure-function relationships and lipid-protein interactions in relation to age, sex, and dry eye symptoms.

Study: HCV and dry eye

Hmph. Dunno what I'm supposed to conclude here. (Don't let anybody cry on your shoulder?)

Hepatitis C and ocular surface disease.

Jacobi C, Wenkel H, Jacobi A, Korn K, Cursiefen C, Kruse FE.
Am J Ophthalmol. 2007 Nov;144(5):705-711. Epub 2007 Sep 17.Click here to read

PURPOSE: To assess the frequency of changes in the ocular surface and the presence of hepatitis C virus (HCV) in tear samples of patients with chronic HCV infection. DESIGN: Prospective, nonrandomized, clinical, interdisciplinary, single-center study. METHODS: Seventy-one patients with previously untreated chronic HCV infection and a control group consisting of 66 patients without systemic HCV infection were enrolled in the trial. The patients with HCV infection were screened for ocular symptoms, visual acuity, and ocular changes. Tear production was measured by the Jones test. Conjunctival impression cytologic analysis was performed. The presence of HCV ribonucleic acid (RNA) in tear and blood samples was determined by quantitative polymerase chain reaction. RESULTS: On examination, systemic HCV infection was present for a median of 30 months. Fifty percent of all HCV patients showed a decrease in tear production measured by the Jones test. Apart from epithelial changes related to dry eye syndrome in 12 patients, two patients presented mild peripheral corneal thinning. Polymerase chain reaction analysis detected HCV RNA in five (10%) of 52 tear samples. HCV RNA levels in tear samples (mean, 1.0 x 10(4) copies/ml) were considerably lower than in blood samples (mean, 5.3 x 10(5) copies/ml). CONCLUSIONS: Dry eye syndrome is the most frequently observed ocular feature in HCV infection. Patients with HCV infection (age range, 21 to 60 years) compared with the controls had a significant lower tear production (P = .05). The presence of HCV RNA in 10% of tear samples emphasizes the potential risk of viral transmission through tears.

Study: Kids, dry eye, systemic disease

Nothing too surprising or remarkable here. Focus is presumably on severe aqueous deficient dry eye which indeed is rare in kids and parents need to be proactive about searching out possible implications and tie-ins with systemic disease. I am disappointed that no mention was made of sclerals in these cases - I think that when you've got developing eyes and dryness severe enough to cause ulcers and loss of BCVA that ought to be a very attractive treatment route to consider.

Management of dry eye related to systemic diseases in childhood and longterm follow-up.

Mac Cord Medina F, Silvestre de Castro R, Leite SC, Rocha EM, de Melo Rocha G.
Acta Ophthalmol Scand. 2007 Nov;85(7):739-44. Epub 2007 Jun 8.

Purpose: Dry eye in children is not common in general practice and is usually referred to tertiary centres for diagnostic confirmation. In the present review we examine the potential causes of dry eye in children and report the management and longterm follow-up of dry eye in childhood with reference to clinical diversity, systemic associations, ocular outcomes and treatment trends. Methods: A retrospective, consecutive case series was studied by evaluating the clinical charts of children with dry eye over a 96-month period. Minimal diagnostic inclusion criteria were presence of ocular surface damage and tear deficiency. Results: Fourteen patients with an age range at presentation of 1-17 years were evaluated. Ten patients were female, four were male and all had bilateral involvement. The most frequent symptoms were red eye, photophobia and low visual acuity (VA). Four patients had corneal ulcers. Two patients had best corrected visual acuity (BCVA) less than or equal to 20 200 at first examination. One of these plus another patient presented with BCVA less than or equal to 20 200 received autologous serum tears and five submitted to conjunctival flaps to preserve the integrity of the eye. Associated systemic conditions were found in all patients and were congenital in six of them. Conclusions: Early manifestations of dry eye in childhood are a potential indication of systemic disease. The ocular condition may be misdiagnosed and correct treatment delayed. Most diseases are bilateral and may jeopardize VA. Systemic investigation, close follow-up and preparing the family for longterm and multidisciplinary treatment are necessary to preserve ocular health and identify systemic associations.

...But while we're talking about kids, let's not forget the more frequent problem of good ol' meibomian gland dysfunction, which sure seems to be on the rise amongst youngsters. Parents, if you want to invest in your kids' eye health... feed them right, don't overdo the drugs, and if they're wearing contacts, make sure you VIGOROUSLY reinforce all doctor instructions about caring for them.

Study: Larch arabi-something and wound healing

Below is an interesting new study that popped up on Medline. Usually I don't get too excited about studies with words of ten syllables other than to take a mental note along the lines of "here's something that might lead to something that eventually ends up in the drug pipeline ten years hence" but this one caught my eye. Larch trees are a little off the beaten track even for dry eye treatment, where we come across everything from snake oil to iguana spit. Plus, anything that talks about "mucoadhesive" properties (i.e. helping lubricants stay on the eye longer) is something I want to know about.

If I knew anything about naturopathy or dietary supplements (I don't) I probably wouldn't have had to google this polysaccharide (I did). Here's a link to an article with more background that I found helpful.

Larch Arabinogalactan for Dry Eye Protection and Treatment of Corneal Lesions: Investigation in Rabbits.
Burgalassi S, Nicosia N, Monti D, Falcone G, Boldrini E, Chetoni P. J Ocul Pharmacol Ther. 2007 Nov 14.

Purpose: The aim of the present study was to investigate the corneal protective and healing properties of arabinogalactan (AG), a natural polysaccharide present in conifers of the genus Larix (Larch). AG was tested in comparison with other two polysaccharides possessing well-established properties in the treatment of dry eye: tamarind seed polysaccharide and hyaluronic acid. Methods: The AG formulation was subjected to the following investigations: rheologic measurements; evaluation of mucoadhesive properties by rheologic interaction with mucin; ferning test; and in vivo evaluation on rabbits, including treatment of an experimental dry eye; evaluation of the preocular retention; and evaluation of healing rate of experimental corneal wound. Results: AG dispersions showed a newtonian nonviscous behavior, eta = 1.6 mPa . s for 10% w/w solution; it possessed good mucoadhesive properties useful for retention on the eye surface. In fact, a prolonged time of residence in rabbit eyes was ascertained using fluorescein-labeled AG. Five percent (5.0%) w/w AG exerted a good protective effect against the appearance of corneal dry spots. It also reduced significantly the healing time of an experimental corneal lesion since 27 h after the first treatment. Conclusions: These findings suggest that AG may be a potential therapeutic product for dry eye protection and for the treatment of corneal wounds.