Wednesday, June 29, 2011

Abstract: Nutritional supplements...

Get a load of that summary. (My highlight, below.) I wonder if the word "novel" has a specific medical definition in this context which is somehow escaping me. It seems to me that MDs and ODs have been pushing flax or fish oil on their dry eye patients forever, certainly since before the (in)famous Harvard tuna study.

Nutritional supplements for dry eye syndrome.
Essential fatty acids have been of interest in the treatment of systemic and ocular diseases, and is most recently of interest in the area of dry eye disease.

Systemic and topical omega-3 fatty acids and omega-6 fatty acids have been used recently as an adjunctive treatment for patients with dry eye disease. They appear to have efficacy against the symptoms of dry eye that many patients experience. This symptom is postulated to be secondary to the anti-inflammatory effects that have been previously described. Although this effect is promising, more investigation is warranted in order to standardize indication for use, and composition and dosing for treatment.

The use of essential fatty acids as a nutritional supplement is a novel treatment for patients with dry eye syndrome.

Curr Opin Ophthalmol. 2011 Jul;22(4):279-82.
Rand AL, Asbell PA.
Mount Sinai School of Medicine, New York, USA.

Abstract: Partial thermal cautery in Sjogrens patients

This is interesting. Though personally my first thought is, if partial occlusion works so well why not replicate it less invasively by using partial occlusion plugs?

Two-year outcome of partial lacrimal punctal occlusion in the management of dry eye related to Sjögren syndrome.
To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjögren syndrome.

Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 ± 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate.

The average lacrimal punctum diameter before the procedure was 0.65 ± 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion.

Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjögren syndrome.

Curr Eye Res. 2011 Jun;36(6):507-12.
Holzchuh R, Villa Albers MB, Osaki TH, Igami TZ, Santo RM, Kara-Jose N, Holzchuh N, Hida RY.
Department of Ophthalmology, Hospital das Clínicas of University of São Paulo, Brazil.

Abstract: Tear meniscus in keratoconic eyes

Tear meniscus analysis with Fourier-domain optical coherence tomography in keratoconus.

To measure the lower tear meniscus dynamics with Fourier domain-optical coherence tomography (FD-OCT) in keratoconus patients without dry eye findings to evaluate the effects of the corneal ectasia on lower tear meniscus parameters, and to determine the most affected meniscus variable from the corneal ectasia in keratoconus.

Prospective, clinical study. Forty-one eyes of 25 keratoconus patients without dry eye and 40 eyes of 20 healthy subjects were included. The lower tear meniscus analysis with FD-OCT, and corneal topography, keratometry, and pachymetry measurements were performed in all eyes. The main outcomes, including the lower tear meniscus height (TMH), depth (TMD), area (TMA), and angle between cornea and the tear meniscus (α-angle), were assessed. The results were compared between the patients and the control subjects.

The average keratometric power was 53.94 ± 5.76 D (between 44.46 to 63.75 D) in keratoconic eyes. It was 43 ± 0.8 D (between 40.50 to 45.94 D) in the controls. The average TMH, TMD, and TMA values did not show any statistically significant difference between the patients and the controls (p = 0.39, p = 0.824, p = 0.516, respectively). However, the average value of the α-angle was significantly higher in keratoconic eyes when compared to controls (p = 0.031). It was positively correlated with the keratometric power (r = 0.577, p = 0.001).

The TMH, TMD, and TMA did not show any change with the corneal protrusion; however, the α-angle had positive correlation with the keratometric power in keratoconic eyes.

Curr Eye Res. 2011 Jun;36(6):528-33.
Sarac O, Soyugelen G, Gurdal C, Bostancı-Ceran B, Can I.
Ankara Ataturk Training and Research Hospital, 2nd Department of Ophthalmology, Ankara, Turkey.

Abstract: How much meibum, with and without MGD

Quantification of human sebum on skin and human meibum on the eye lid margin using Sebutape®, spectroscopy and chemical analysis.

The purpose of this study was to determine if the variability in the amount of lid margin meibum is from donor-to-donor or from day-to-day variations and to determine if meibum from donors with meibomian gland dysfunction (MGD) had altered levels of casual eyelid meibum or skin sebum.

Lipid absorbent Sebutape(®) was used to collect sebum or meibum. Samples were collected from six donors without dry eye and 21 donors with MGD. Lipid absorbed to Sebutape(®) was quantified using infrared and visible absorbance spectroscopy.

The amount of sebum from donors with MGD and donors without MGD was not significantly different. The amount of casual meibum from normal donors was 50% lower than that for donors with MGD using the spectroscopic assay, but was not significantly different using the chemical assay. The frequency and bandwidth of the infrared carbonyl band from sebum samples was significantly higher than that for meibum samples which indicates the carbonyls are in a different "dielectric" environment. The average relative standard deviation for the casual level of meibum and the level of sebum suggests that the 49% relative standard deviation of casual meibum measured once for each subject using a meibometer may have been due to day-to-day variations and not necessarily due to variations between individuals. The values measured using two different assays were correlated and therefore reliable.

The idea that tear film instability is associated with the quantity of lid margin lipid is not supported by this study because the quantity did not change with MGD. The amount of forehead sebum was not a bio-marker for MGD. Sebutape(®) is an excellent vehicle to remove tenths of a milligram of meibum from the eyelid and sebum from skin for experimental analysis.

Curr Eye Res. 2011 Jun;36(6):553-62.
Ashraf Z, Pasha U, Greenstone V, Akbar J, Apenbrinck E, Foulks GN, Borchman D.
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.

Abstract: Lotemax and Zylet users take note

This is an interesting little study. They looked at people whose intraocular pressure rose while on a "mild" steroid and reviewed how long they were on it before their pressure rose and what happened in the end. 28% had a history of glaucoma or something related but that still leaves a large majority of patients with no adverse history. The median length of treatment before elevated IOP was noted was 55 days.

For those of you on mild steroids, the moral of this story is you should check in with your doctor about being monitored for IOP elevation on a regular basis - not just once in the beginning. Honestly, I am horrified at some of the stories I hear from time to time of people being put on steroids and having prescriptions refilled regularly without ever having their IOP checked. I'm sure many doctors are doing a great job but obvious some are doing a really poor job at this.

Just because it's not Pred Forte doesn't mean you get off scot free when it comes to IOP risk from steroids.

Intraocular pressure elevations with loteprednol etabonate: a retrospective chart review.

Abstract Purpose:
Ocular corticosteroids can cause elevations in intraocular pressure (IOP). The purpose of this study was to characterize the timing and severity of IOP elevations in patients receiving loteprednol etabonate 0.5% or loteprednol etabonate 0.5%/tobramycin 0.3%.

A retrospective chart review was conducted at 5 academic and private practices. Any patient who experienced an elevation in IOP ≥5 mm Hg while using loteprednol etabonate or loteprednol etabonate/tobramycin was eligible for inclusion in the study. Data collected included patient demographics, medical and ophthalmic history, concomitant medications, reason for treatment, IOP, and medical and surgical interventions.

Fifty patients experienced IOP elevations after use of topical loteprednol etabonate and were included in the study. The mean (standard deviation [SD]) patient age was 58.8 (20.3) years and 66% were women. The most common reasons for prescribing loteprednol etabonate were dry eye (30%), postoperative therapy (22%), and allergic conjunctivitis (16%). Before treatment, 28% of patients had a history of open-angle glaucoma or ocular hypertension. Mean (SD) IOP before treatment was 15.5 (3.2) mm Hg and increased to a mean (SD) of 24.7 (6.5) mm Hg, a statistically significant increase of 9.2 (SD: 5.8; range: 5-29) mm Hg (P < 0.0001). The median duration of treatment with loteprednol etabonate at the time of observed IOP elevation was 55 days (range: 3 days to 3 years). Twenty-four percent of patients required IOP-lowering medications and 8% required surgery to control the elevated IOP.

Alternatives to corticosteroids should be considered when long-term treatment is required for an ocular surface condition.

J Ocul Pharmacol Ther. 2011 Jun;27(3):305-8. Epub 2011 May 16.
Rajpal RK, Digby D, D'Aversa G, Mah F, Hollander DA, Conway T.
1 SeeClearly Vision , McLean, Virginia.

Abstract: Confocal microscopy of MGs in contact lens wearers

In Vivo Confocal Microscopy of Meibomian Glands in Contact Lens Wearers.

To evaluate by in vivo laser scanning confocal microscopy (LSCM) the morphological changes of the Meibomian glands (MGs) and the status of periglandular inflammation in contact lens wearers (CLWs) and to investigate the correlations between clinical and confocal findings.

Twenty CLWs and 20 age- and gender-matched control subjects were consecutively enrolled. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time, fluorescein and lissamine green staining, and Schirmer test. LSCM of the MGs were performed to determine the cell density of the mucocutaneous junction epithelium, acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, and inhomogeneous appearance of the glandular interstice and acinar wall.

All clinical parameters showed statistically significant differences between groups (P <0.01, Mann-Whitney U test) except the Schirmer test. Confocal data (Mann-Whitney U test) showed significantly decreased basal epithelium cell density ( P <0.01), lower acinar unit diameters (P <0.05), higher glandular orifice diameters (P <0.05), greater secretion reflectivity (P <0.01), and greater inhomogeneity of the periglandular interstices (P <0.05) in CLWs compared to controls. The duration of contact lens wear was correlated with the acinar unit diameters (P < 0.05, Spearman).

Morphological changes of the MGs shown by LSCM were interpreted as signs of MG drop-out, duct obstruction, and glandular inflammation. A comprehensive LSCM evaluation of the ocular surface in CLWs could better clarify the role of MG drop-out and eyelid margin inflammation on the pathogenesis of CL-induced dry eye.

Invest Ophthalmol Vis Sci. 2011 May 12. [Epub ahead of print]
Villani E, Ceresara G, Beretta S, Magnani F, Viola F, Ratiglia R.
Università degli Studi di Milano. UO Oculistica Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.

Abstract: Mucosal microvilli in dry eye patients with chronic GVHD

Mucosal microvilli in dry eye patients with chronic GVHD.

The ocular surface is a frequent target tissue of mucosal chronic GVHD (cGVHD). We investigated the histopathological features of the conjunctival microvilli in patients with cGVHD. Conjunctival tissue specimens from patients with cGVHD or Sjögren's syndrome (SS) or from healthy individuals were examined by light microscopy and EM, impression cytology, and immunohistochemistry. The cGVHD conjunctivae showed significantly more metaplasia and fewer goblet cells than the SS and normal conjunctivae. Abundant CD8(+) T cells infiltrated the basal epithelia in the cGVHD conjunctiva. The microvilli per standard epithelial unit and the secretory vesicles were counted by analyzing electron micrographs. The mean number of mucosal microvilli was significantly lower in the cGVHD than that in the SS or normal specimens, and the microvilli were significantly shorter, with a smaller height-width ratio. The mean number of secretory vesicles was also significantly lower, and the membrane-spanning mucin thinner, in the cGVHD compared with the SS and normal specimens. Thus, the conjunctival mucosal microvilli of cGVHD patients were significantly different in number and morphology from those of SS and normal subjects. These may be important factors affecting the stability of the tear-film layer and its contribution to cGVHD-related dry eye.

Bone Marrow Transplant. 2011 May 16. [Epub ahead of print]
Tatematsu Y, Ogawa Y, Shimmura S, Dogru M, Yaguchi S, Nagai T, Yamazaki K, Kameyama K, Okamoto S, Kawakami Y, Tsubota K.
Department of Ophthalmology, The Keio University School of Medicine, Tokyo, Japan.

Drug updates: Rebamipide

This is not new news, but I think I missed it along the way. Otsuka has applied for regulatory approval in Japan for Rebamipide following positive Phase III data, but is supposedly somewhere in Phase II in the US. Have not heard any positive noises about US prospects on this drug for a long time.

May 6 press release

Phase III Study Results for Rebamipide Ophthalmic Suspension for Dry Eye Announced at ARVO 2011

Tokyo, Japan, May 6, 2011 -- Otsuka Pharmaceutical Co., Ltd. today announced results of a phase III clinical study of its in-development dry eye treatment "rebamipide ophthalmic suspension" for dry eye patients, at ARVO* 2011 (May 1-5, 2011, Fort Lauderdale, Florida, USA).

* ARVO: Association for Research in Vision and Ophthalmology
The phase III study was conducted in Japan on 188 patients with signs and symptoms of dry eye, to examine the efficacy and safety of 2% rebamipide ophthalmic suspension in comparison with 0.1% sodium hyaluronate ophthalmic solution. As the results of the study, it was confirmed that in addition to the improvement in corneal-conjunctival damage in patients with dry eye, rebamipide ophthalmic suspension also showed improvements in subjective symptoms such as foreign body sensation and eye pain and in subject's overall treatment impressions.

Based upon the results of this study, in October 2010 Otsuka Pharmaceutical applied for regulatory approval to manufacture and market rebamipide ophthalmic suspension in Japan. In the U.S., a phase II program with co-development partner Acucela Inc. is ongoing.

Based on its corporate philosophy of "Otsuka-people creating new products for better health worldwide," Otsuka Pharmaceutical Co., Ltd. is dedicated to contributing to the health of people around the world.

About 5 weeks of updates to follow...

Sorry I've gotten so behind. The next several posts will be catching up on all June and even a little bit of May dry eye news.