Volume 14, Number 5
Monday, February 3, 2014


In this issue: (click heading to view article)
######### Potential Links of Age-Related Changes of Cystatin C Expression and Polarized Secretion by RPE to AMD

######### Impact of Retinal Blood Flow on OAG in Patients with and without Diabetes

######### Identifying Changes in Subfoveal Choroidal Thickness and Choroidal Extravascular Density Using SD-OCT Before and After Hemodialysis
######### Treatment of AKC with Tacrolimus Ointment
######### Briefly


Potential Links of Age-Related Changes of Cystatin C Expression and Polarized Secretion by RPE to AMD

Cystatin C, a potent cysteine proteinase inhibitor, is abundantly secreted by the retinal pigment epithelium (RPE) and may contribute to regulating protein turnover in the Bruch's membrane. A variant associated with increased risk of developing age-related macular degeneration (AMD) and Alzheimer's disease presents reduced secretion levels from RPE. The purpose of this study was to analyze the effects of age and the accumulation of advanced glycation end-products (AGEs) on the expression and secretion of cystatin C by the RPE.

Confluent monolayers of human fetal RPE (hfRPE) cells were cultured using an in vitro model mimicking extracellular AGE accumulation. Cystatin C expression, secretion and its polarity were analyzed following culture on AGE-containing Bruch's membrane mimics (AGEd vs non-AGEd). Additionally, monolayer barrier properties were assessed by transepithelial resistance measurements and the relative level of cystatin C protein expression in human RPE in situ was assessed immunohistochemically in relation to age.

It was reported that AGE-exposed RPE monolayers presented significantly decreased cystatin C expression and secretion. Basolateral secretion was fully established by week eight in non-AGEd conditions, and in AGEd cultures, polarity of secretion was impaired despite maintenance of physiological barrier properties of the monolayer. Furthermore, in the macula region of RPE/choroid segments from human eyes, the level of cystatin C protein was reduced with increasing donor age.

It was determined that exposure to AGEs reduces expression of cystatin C and affects its normal secretion in cultured RPE. Age-related changes of cystatin C in the RPE from the posterior pole may compromise its extracellular functions, potentially contributing to AMD pathogenesis.

SOURCE: Kay P, Yang YC, Hiscott P, et al. Age-related changes of cystatin C expression and polarized secretion by retinal pigment epithelium: potential age-related macular degeneration links. Invest Ophthalmol Vis Sci. 2014; Jan 23.[Epub ahead of print].

Impact of Retinal Blood Flow on OAG in Patients with and without Diabetes

The authors of this study sought to evaluate the impact of retinal blood flow on optic nerve head (ONH) morphology in patients with open-angle glaucoma (OAG) with and without diabetes mellitus.

They assessed 66 patients with OAG (14 with diabetes mellitus, 52 without diabetes mellitus) at baseline and at three-year follow-up for retinal capillary blood flow using confocal scanning laser Doppler and ocular structure using Heidelberg retinal tomography and optical coherence tomography.

The authors found change in retinal tissue with zero blood flow in the superior and inferior retina to have a strong correlation with ONH changes in diabetic patients (r≥0.90, p≤0.03); however, they found no relation in the nondiabetic cohort. They also observed significant changes in inferior mean flow that strongly correlated with changes in cup area (r=0.97, p=0.0029), cup/disc area ratio (r=0.96, p=0.0070), linear cup/disc ratio (r=0.93, p=0.0172), rim area (r=–0.97, p=0.0036), and rim volume (r=–0.95, p=0.0084) in diabetic patients only, while changes in the superior mean flow were only significantly associated with cup area (r=–0.30, p=0.0498), cup volume (r=–0.36, p=0.0178), and rim volume (r=0.35, p=0.0193) in nondiabetic patients.

In this cohort of patients with OAG, changes in retinal capillary blood flow correlated more strongly with changes in ONH morphology in patients with DM than in those without diabetes mellitus. These data suggest that changes in retinal blood flow may play a larger role in glaucomatous ONH progression in patients with OAG with diabetes mellitus.

SOURCE: Lee E, Harris A, Siesky B, et al. The influence of retinal blood flow on open-angle glaucoma in patients with and without diabetes. Eur J Ophthalmol. 2014;Dec 20. [Epub ahead of print].


Identifying Changes in Subfoveal Choroidal Thickness and Choroidal Extravascular Density Using SD-OCT Before and After Hemodialysis

Investigators in South Korea examined the changes in the subfoveal choroidal thickness (SFCT) and choroidal density using spectral domain optical coherence tomography (SD-OCT) before and after hemodialysis.

Included in the study were 28 eyes of 19 patients with chronic renal failure (CRF) undergoing hemodialysis. The investigators performed ophthalmologic examinations including SD-OCT one hour before and after hemodialysis. They measured subfoveal choroidal thickness manually using Image J software, and evaluated the relationships between the change in subfoveal choroidal thickness and in the systemic parameters following hemodialysis. They also evaluated the changes in choroidal extravascular density of the OCT image after hemodialysis by comparing the brightness value obtained with Adobe Photoshop software.

According to the study investigators, the mean subfoveal choroidal thickness of all eyes increased significantly from 276.94 ± 58.73 µm to 288.29 ± 65.57 µm (p=0.003). And in the univariate generalized estimating equation (GEE), the subfoveal choroidal thickness increased significantly after hemodialysis (p=0.006). After adjusting for age, gender and other significant factors in univariate analysis, the investigators noted that the subfoveal choroidal thickness increased significantly after hemodialysis (p=0.032). Moreover, they associated the decrease in systolic blood pressure (SBP) with the increase in subfoveal choroidal thickness (p=0.013). The choroidal extravascular density of OCT image increased after hemodialysis (p<0.001) and the mean change was 12.35 ± 9.72. br>

To conclude, in the SD-OCT image, the subfoveal choroidal thickness became thicker and the choroidal extravascular density increased following hemodialysis in patients with CRF. The investigators associated the decrease in SBP after hemodialysis with an increase in subfoveal choroidal thickness. They determined that the choroidal autoregulatory control of ocular hemodynamic change and shifting of fluid and molecules between the blood and choroidal interstitium might be involved in the mechanism of these choroidal changes.

SOURCE: Jung JW, Chin HS, Lee DH, Yoon MH, Kim NR. Changes in subfoveal choroidal thickness and choroidal extravascular density by spectral domain optical coherence tomography after haemodialysis: a pilot study. Br J Ophthalmol. 2014; 98(2):207–212.


Treatment of AKC with Tacrolimus Ointment

In Saudi Arabia, researchers conducted the following prospective, nonrandomized, noncontrolled case series to evaluate the long-term clinical outcomes of 0.1% tacrolimus dermatologic ointment (Protopic) in cases of refractory atopic keratoconjunctivitis (AKC). They found that tacrolimus dermatologic ointment is a potentially safe and effective treatment for AKC cases refractory to standard treatment and may substitute for steroid treatments aimed at controlling disease activity.

The researchers followed 22 eyes from 11 patients with severe AKC who were treated with 0.1% tacrolimus ointment prospectively. The mean age of the patients was 32.27 ± 12.7 years (range, 19 to 61 years). Each patient completed a follow-up period of at least 48 months, during which the researchers assessed the signs and symptoms of AKC. They also recorded changes in the total scores of signs and symptoms from baseline at each visit. The main outcome measure was the clinical response to topical tacrolimus treatment.

The researchers noted that dramatic improvements in clinical signs and symptoms were achieved one week after starting topical tacrolimus treatment, and complete clinical resolution was observed in almost all patients six weeks after starting treatment. Treatment was gradually reduced, with increasing intervals between applications, and eight patients remained asymptomatic for up to three years, although recurrence occurred in three patients who attempted to discontinue treatment. All patients complained of a mild burning sensation upon application of the ointment. No additional medications were required to provide relief, and no patient discontinued treatment because of adverse drug effects. No drug-related ocular complications were encountered, and no significant changes in visual acuity or refraction were documented.

SOURCE: Al-Amri AM. Long-term follow-up of tacrolimus ointment for treatment of atopic keratoconjunctivitis. Am J Ophthalmol. 2014;157(2):280–286.

  • AERIE PHARMACEUTICALS INITIATES PHASE IIB STUDY OF PG324 TO TREAT PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION. Aerie Pharmaceuticals Inc. has begun dosing of the first patients enrolled in its Phase IIb study of PG324, a novel, fixed-combination of Aerie's AR-14423 and the prostaglandin analogue latanoprost. The 28-day trial is expected to enroll roughly 300 patients with either glaucoma or hypertension and will compare two concentrations of PG324 to latanoprost and to AR-13324, all dosed once daily. The efficacy endpoint will be superiority of PG324 to each of its components, as measured by the lowering of mean diurnal intraocular pressure on day 28 compared to baseline. Aerie currently expects topline results of this trial in mid-2014. Further details can be found at www.aeriepharma.com.
  • FDA GRANTS FINAL APPROVAL OF HI-TECH'S ANDA FOR BROMFENAC OPHTHALMIC SOLUTION. According to Hi-Tech Pharmacal Co. Inc., the FDA has granted final approval of the company's Abbreviated New Drug Application (ANDA) for bromfenac ophthalmic solution, 0.09% (Once-A-Day), the generic for ISTA Pharmaceuticals' Bromday ophthalmic solution, 0.09%. The product is used to treat postop inflammation and reduce ocular pain in patients who have undergone cataract surgery. Hi-Tech plans to launch the product immediately. Visit www.hitechpharm.com for additonal details.
  • ACCUTOME EXPANDS SERIES OF SURGICAL KNIVES. Accutome has added to its AccuSharp Series of ophthalmic surgical knives with the new M-series Angled Disposable Slit Knives. Made from stainless steel and featuring a new “teardrop” bevel design for superior sharpness, the new knives provide surgeons with a 2.0-mm depth indicator to help generate proper wound architecture. The M-series comes in a variety of sizes compatible with the latest microincision cataract procedures. Additionally, each blade is locked into a protective plastic case. Learn more at www.accutome.com.

  • PREVENT BLINDNESS ANNOUNCES CALL FOR APPLICATIONS FOR 2014 JOANNE ANGLE INVESTIGATOR AWARD. In a recent press release, Prevent Blindness announced the call for applications for its 2014 Joanne Angle Investigator Award, which is a research grant provided annually to a public health project that seeks to help save sight. The award provides funding for research investigating public health related to eye health and safety. Applications will be accepted in the following priority areas in adult vision, children's vision or eye injury: burden/economic aspects of eye disease/vision loss on society, best practices to integrate vision screening/follow-up care to system care access, and vision program effectiveness/evaluation. The deadline to submit applications is March 31, 2014. Grants are for a one-year period, up to $30,000, reviewed by a panel of scientists, and commence on July 1, 2014.

  • QUANTEL MEDICAL'S OPTIMIS FUSION RECEIVES CE MARK APPROVAL. Quantel Medical has been given CE Mark approval for its Optimis Fusion integrated laser platform, which combines selective laser trabeculoplasty photoregeneration therapy and traditional YAG photodisruption treatments to offer ophthalmologists a versatile armamentarium for treating both cataract and glaucoma. The Fusion integrates smoothly with Quantel's Vitra Monospot and Multispot pattern-scanning retina laser systems, offering comprehensive treatment options for multi-specialty practices to treat glaucoma, cataract and retina conditions in one laser platform. The company is expecting FDA approval in 2014, but in the meantime, it will immediately begin commercialization in all CE Mark-approved countries. To learn more, visit Quantel's website.

  • HAAG-STREIT TO OFFER JOHN WEISS SURGICAL INSTRUMENTS. Haag-Streit USA has joined with John Weiss & Son Ltd. to be the exclusive supplier of John Weiss stainless steel and titanium hand-held surgical instruments in the United States. Read Haag-Streit’s press release for additional information.

  • GRAYBUG TO PARTICIPATE IN GLAUCOMA 360 CONFERENCE. GrayBug LLC recently reported that it will participate in the Glaucoma 360 New Horizons Forum being held on February 7th at The Palace Hotel in San Francisco. The meeting, presented by Glaucoma Research Foundation, brings together key clinical, industry, financial and regulatory leaders in a unique exchange on research innovation and advances in glaucoma treatment. GrayBug's president and CEO will present on the company's development of delivery systems for controlled release of therapeutics for the treatment of glaucoma and other intraocular diseases.

  • SKUTA BEGINS TERM AS AAO PRESIDENT. Nationally recognized glaucoma specialist Gregory L. Skuta, MD, has begun his one-year term as the 117th president of the American Academy of Ophthalmology. He is president and CEO of the Dean McGee Eye Institute and serves as the Edward L. Gaylord professor and chair of the University of Oklahoma College of Medicine's department of ophthalmology. In his role as president of the Academy, Dr. Skuta will focus on important issues and initiatives for the profession, including ophthalmic education; physician reimbursement and patient access; funding for vision research; the introduction o the Academy's IRIS Registry; and preparation by ophthalmologists for the implementation of ICD-10.



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