Volume 13, Number 7
Monday, February 18, 2013


In this issue: (click heading to view article)
######### From the Editor: The Right of Free Speech

######### Influence of Statins on the Development and Progression of AMD

######### Genetic Determinants of MPOD in Women
######### A Closer Look at Inflammatory Biomarkers and Risk of Diabetic Retinopathy
######### Ocular Flora Changes in Eyes Exposed to Ophthalmic Antibiotics
######### Briefly

From the Editor: The Right of Free Speech

Some years ago, I did a modest amount of speaking for both pharmaceutical and device companies. I enjoyed meeting and interacting with colleagues throughout the country. It was my hope that I could impart a bit of my experience and knowledge regarding my success with a product or device. In reality, most times the attendees learned a bit and I learned something as well. What (in reality) was taking place was interaction among highly educated physicians about ways we could further help our patients.

Over time though, it morphed into an “on script,” somewhat robotic presentation that no one really cared to listen to. Attendance dropped off. The free flow of information withered on the vine. Eventually, things deteriorated to the point that I was required to point out that any question related to a potential off-label use of a drug or device was taboo. I needed to respond to it briefly and redirect the conversation back to the script. How sad. It is the reason I stopped speaking.

Recently, I was a bit delighted to see that a three-judge U.S. appeals court (essentially) ruled that the FDA, in restricting an open and intelligent conversation among physicians, was in violation of free speech. How refreshing but sad at the same time. Why does it take an appeals court to give the okay for physicians to debate and discuss treatments we can offer that may help our patients? Physicians are extremely educated, caring individuals who have their patients' best interests at heart. We have the experience and independence to come to the right decision about what is best for our patients.

Stephen Pascucci, MD, FACS

Register now at http://www.revophth.com/GlaucMgmt2013

Influence of Statins on the Development and Progression of AMD

In the quest to determine whether statins are associated with the development or progression of age-related macular degeneration (AMD), researchers reviewed a large, national insurance claims database to identify individuals aged 60 years or older who were enrolled for two or more years and had one or more visits to an eye-care provider.

They also reviewed prescription claims for statins within a 24-month look-back period as well as outpatient lipid laboratory values. They used Cox regression analysis to determine whether statin use was associated with the development of nonexudative or exudative AMD or progression from nonexudative to exudative AMD.

Of the 107,007 beneficiaries eligible for the nonexudative AMD analysis, the researchers noted that 4,647 incident cases of nonexudative AMD occurred. They also found 792 incident cases of nonexudative AMD among the 113,111 beneficiaries eligible for the exudative AMD analysis. They reported that of the 10,743 beneficiaries with known nonexudative AMD eligible for the progression model, 404 progressed to exudative AMD during their time in the plan. Following multivariable analysis, statin use was not associated with the development of nonexudative AMD (p>0.05). However, statin use of more than 12 months was associated with an increased hazard for developing exudative AMD (p<0.005). Furthermore, among those taking statins, only enrollees with the highest lipid levels had an increased hazard of developing exudative AMD (p<0.05).

In conclusion, in those with elevated lipid levels, more than one year of statin use was associated with an increased hazard for exudative AMD. Lipid status influences the relationship between statins and the risk of AMD. Because of a number of limitations in study design, these observations warrant further study and should not be the rationale for any changes in the use of statins to treat dyslipidemias.

SOURCE: VanderBeek BL, Zacks DN, Talwar N, et al. Role of statins in the development and progression of age-related macular degeneration. Retina. 2013;33(2):414–422.

Genetic Determinants of MPOD in Women

The authors of the following study aimed to investigate genetic determinants of macular pigment optical density (MPOD) in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.

Of the 2,005 CAREDS participants, 1,585 had MPOD measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding and cleavage of carotenoids directly, or via lipid transport. The authors tested SNPs individually for associations with MPOD using least-squares linear regression.

According to the authors, 21 SNPs from 11 genes were associated with MPOD (p≤0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5 and LIPC), long-chain omega-3 fatty acid status (EVOVL2, FADS1 and FADS2) as well as various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA=0.029, p=2.2x10–4). The authors reported that conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes and dietary intake of fiber resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. They noted that variation in these single-gene polymorphisms accounted for 5% of the variability in MPOD (p=3.5x10–11).

These results support that MPOD is a multifactorial phenotype associated with variation in genes related to carotenoid transport, uptake and metabolism, independent of known dietary and health influences on MPOD.

SOURCE: Meyers KJ, Johnson EJ, Bernstein PS, et al. Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study. Invest Ophthalmol Vis Sci. 2013; Feb 12. [Epub ahead of print].

A Closer Look at Inflammatory Biomarkers and Risk of Diabetic Retinopathy

This multicenter, randomized, controlled clinical trial sought to determine whether baseline levels of high-sensitivity C-reactive protein (hsCRP) and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort.

The DCCT population consisted of 1,441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1 (VCAM-1) and tumor necrosis factor α receptor 1 in stored baseline blood samples were measured. Additionally, the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1 and tumor necrosis factor α receptor 1 with incident DR endpoints ascertained from grading of standardized seven-field stereoscopic retinal color photographs taken at baseline and every six months during follow-up were assessed.

After adjustment for randomized treatment assignment and other factors, a statistically significant association between hsCRP and risk of CSME was observed, with a relative risk (RR) for the top vs. bottom quintile of 1.83 (95% CI, 0.94–3.55; p for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs. bottom quintile of hsCRP level was 1.78 (95% CI, 0.98–3.25; p for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs. bottom quintiles as 1.50 (95% CI, 0.84–2.68; p for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR endpoints.

After adjusting for known risk factors, this study demonstrates that increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

SOURCE: Muni RH, Kohly RP, Lee EQ, et al. Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the Diabetes Control and Complications Trial. JAMA Ophthalmol. 2013; Feb 7. [Epub ahead of print].

Ocular Flora Changes in Eyes Exposed to Ophthalmic Antibiotics

Investigators conducted the following prospective, controlled, longitudinal study with a one-year follow-up to determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics.

They included 48 eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization. Patients received four consecutive monthly unilateral intravitreal injections and were then treated as needed. The investigators randomized each patient to one of four antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and patients used only their assigned antibiotic for four days following each injection. Conjunctival cultures of the treated eye and untreated eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Main outcome measures were changes in bacteria composition of the conjunctiva over time.

The study investigators observed that in azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (p<0.01) and 4.5% (p<0.01), respectively, after azithromycin exposure. They also found that in fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S. epidermidis and S. aureus, respectively, but these percentages increased to 63.4% (p<0.03) and 13% (p=0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of Gram-negative species decreased from 8.7% at baseline to 1.6% (p<0.05) in fluoroquinolone-treated eyes. The percentage of S. epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (p<0.01) or fluoroquinolone-treated eyes (p<0.01).

To conclude, the percentage of S. epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and, to a lesser degree, fluoroquinolone antibiotics, at the expense of other commensal flora.

SOURCE: Dave SB, Toma HS, Kim SJ. Changes in ocular flora in eyes exposed to ophthalmic antibiotics. Ophthalmology. 2013; Feb 13. [Epub ahead of print].

  • FDA ISSUES 510(k) CLEARANCE TO VICTUS FEMTOSECOND LASER PLATFORM FOR ARCUATE INCISION PROCEDURE. Bausch + Lomb recently announced that its VICTUS Femtosecond Laser Platform received 510(k) clearance from the FDA for the creation of penetrating arcuate cuts/incisions in the cornea in patients undergoing cataract surgery or other ophthalmic treatment requiring penetrating arcuate cuts/incisions in the cornea. Bausch + Lomb Technolas (Technolas Perfect Vision GmbH) has been installing VICTUS systems in leading surgery centers globally since it received the CE mark in Europe in November 2011 and U.S. FDA clearance in July 2012. The platform is currently approved for the creation of a corneal flap in patients undergoing LASIK surgery and anterior capsulotomy during cataract surgery, as well as penetrating arcuate incisions in the United States. In Europe, the VICTUS platform is approved for the aforementioned procedures as well as INTRACOR, capsulotomy and lens fragmentation. Click here for additional information.
  • UCLA GETS GREEN LIGHT TO BEGIN PHASE I/II STUDY USING RPE CELLS TO TREAT MYOPIA. Advanced Cell Technology (ACT) Inc.'s clinical partner, the University of California, Los Angeles, has received approval of its Investigator Investigational New Drug (IND) Application with the FDA to initiate a Phase I/II study using ACT's retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) to treat myopia. According to ACT, the primary focus of the study will be to evaluate the safety in patients with severe myopia of the type that causes fissures in the RPE layer of the eye. The clinical trial will follow a protocol similar to the company’s three other human clinical trials in the United States and Europe using hESC-derived RPE cells to treat forms of macular degeneration. The prospective, open-label study will enroll 12 patients, with cohorts of three patients in an ascending dosage format, and is designed to determine the safety and tolerability of hESC-derived RPE cells following sub-retinal transplantation into patients with myopia at 12 months, the study’s primary endpoint. To learn more, visit www.advancedcell.com.
  • ARGUS II SYSTEM RECEIVES FDA APPROVAL. Second Sight Medical Products Inc.'s Argus II Retinal Prosthesis System (“Argus II”) has received U.S. market approval from the FDA to treat individuals with late-stage retinitis pigmentosa (RP). In September 2012, a unanimous recommendation by the FDA's Ophthalmic Devices Advisory Panel made the product available to treat this patient population in the United States. Argus II is intended to provide electrical stimulation of the retina to induce visual perception in blind individuals with RP and has the capacity to offer life-changing visual capabilities to those currently unable to see anything except extremely bright lights at best. With the FDA's approval, the Argus II is slated to be available later this year in clinical centers across the country. Learn more at www.2-sight.com.
  • FDA CLEARS iCAM AND NORMATIVE DATABASE FOR iVUE SD-OCT. Optovue has received FDA 510(k) clearance of the Normative Database for the iVue SD-OCT system, which provides analysis information to be used as a clinical reference to aid in the diagnosis and management of ocular health and disease, as well as for its latest product, the iCam Non-Mydriatic, compact fundus camera. The company says that the addition of the Normative Database enhances iVue's comprehensive suite of clinical applications for retina, optic disc and anterior segment. The diagnostic tool provides quantitative comparisons of the retina, retinal nerve fiber layer, ganglion cell complex and optic disc measurements to aid the practitioner in the evaluation of various ocular pathologies. Once scans are captured, the normative comparison analysis adjusts for the patient's age, optic disc size (for optic nerve head scans only) and scan signal strength. The Normative Database is included with any iVue SD-OCT system purchase and a new software update—expected in early March—will be provided free of charge to all current iVue owners of record. Optovue's iCam camera produces 45° color fundus images of the eye as well as external ocular structures and includes a variety of functions and features that produce high-quality image documentation and management of ocular health. A 12-bit CCD sensor provides deep, rich colors with low noise and an LED light source reduces peak energy to the eye as well as longer life. Visit the company's website to read more.
  • ALLERGAN LAUNCHES PRESERVATIVE-FREE LUBRICANT EYE DROPS. Allergan Inc. recently announced the launch of REFRESH OPTIVE Advanced Preservative-Free Lubricant Eye Drops. The company says that the drop features the same scientifically advanced formula as REFRESH OPTIVE Advanced, but without the use of a preservative. The triple-action formula of REFRESH OPTIVE Advanced Preservative-Free stabilizes the lipid layer to help reduce tear evaporation, hydrates the aqueous layer and provides an advanced lubricating and protective shield to the mucin layer, while further protecting epithelial cells from hypertonic stress. The drop is available in 30-count single-use vials, may be used in combination with dry eye prescription therapies and does not require shaking prior to use. Additional information can be found at www.refreshbrand.com.
  • LEONARD APT, FOUNDING MEMBER OF THE JULES STEIN EYE INSTITUTE, DIES AT AGE 90. Leonard Apt, MD, founding member of the Jules Stein Eye Institute at the University of California, Los Angeles, and an emeritus professor of ophthalmology, died February 1, 2013 after a brief illness. He was an internationally respected UCLA eye surgeon who devoted his career to preventing blindness in children. Dr. Apt co-developed an inexpensive antiseptic drop that substantially reduced the incidence of blindness in children in developing countries. Additionally, he and long-time collaborator Dr. Sherwin Isenberg identified povidone-iodine as a safe topical antimicrobial agent.


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