Volume 14, Number 9
Monday, March 3, 2014


In this issue: (click heading to view article)
######### Growth of GA on Fundus Autofluorescence and Polymorphisms of CFH, CFB, C3, FHR1-3 and ARMS2 in AMD
######### SD-OCT vs. SS-OCT in the Measurement of Choroidal Thickness in Normal Eyes
######### Retinal Vascular Abnormalities in Neovascular AMD
######### Use of Once-Daily Low-Dose Doxycycline to Treat Ocular Rosacea
######### Briefly

Growth of GA on Fundus Autofluorescence and Polymorphisms of CFH, CFB, C3, FHR1-3 and ARMS2 in AMD

Identification of the genetic risk factors that contribute to geographic atrophy (GA) could lead to advancements in interventional trials and/or therapeutic approaches for combating vision loss. Investigators in Spain performed this prospective, controlled, multicenter study to determine whether single-nucleotide polymorphisms (SNPs) are associated with the presence and progression of established GA in age-related macular degeneration (AMD).

Participants consisted of 154 patients with GA/AMD and 141 age-matched control participants at eight Spanish hospitals. The investigators collected samples of DNA to analyze SNPs within AMD-related genes (CFH, CFB, C3, FHR1-3 and ARMS2). They also used fundus autofluorescence imaging was used to evaluate GA progression during a two-year period in 73 patients with GA/AMD. Finally, they used logistic regression to analyze the associations of SNPs, age, body mass index and cigarette smoking with the rate of progression and relative growth of GA.

This case-control analysis revealed a significant (p<0.05) association between the presence of GA and SNPs within CFH, ARMS2 and FHR1-3, the study investigators noted. Moreover, they found that logistic regression analysis identified significant associations of the rate of progression with genetic polymorphisms (CFH-402His [p=0.04] and CFH-62Ile [p=0.04]) and demographic factors (sex [p=0.02] and age [p=0.02]), whereas relative growth was associated with one polymorphism (CFB-32Gln [p=0.04]).

Their findings confirm that genetic risk factors related to the presence of GA are not identical to those associated with GA progression. In fact, they demonstrate that gene variants of CFH and CFB, as well as demographic risk factors, confer significant risk for GA progression (both rate of progression and relative growth) within a Spanish population.

SOURCE: Caire J, Recalde S, Velazquez-Villoria A, et al; for the Spanish Multicenter Group on AMD. Growth of geographic atrophy on fundus autofluorescence and polymorphisms of CFH, CFB, C3, FHR1-3, and ARMS2 in age-related macular degeneration. JAMA Ophthalmol. 2014;Feb 20. [Epub ahead of print].

SD-OCT vs. SS-OCT in the Measurement of Choroidal Thickness in Normal Eyes

The authors of the following prospective, cross-sectional, single-center study aimed to compare spectral-domain optic coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) in the study of choroidal thickness (CT) in healthy eyes.

They included 82 healthy eyes of 46 patients were included and in a single session, Topcon 3D-2000 SD-OCT and 1050 nm SS-OCT prototype devices were used to perform OCT scans using a single line protocol. Two masked investigators independently, manually determined 13 CT measurements consisting of one subfoveal (SFCT), and six measurements on either side of the fovea (nasal and temporal) taken every 500 µm apart. The mean CT (MCT) was the mean average of these 13 measurements.

According to the authors, SD-OCT was able to reproducibly measure the CT in 74.4% of eyes versus 100% with SS-OCT (p<0.05; Fisher's Exact test). In those eyes measured by both systems, mean SFCT was 279.4 ± 96.9 µm (range, 84 to 506) with SD-OCT vs. 285.7 ± 88.9 µm (range 130 to 527) with SS-OCT (p=0.11; Student's t test paired data). Mean MCT was 243.8 ± 78.8 µm (range 103.6 to 433.2) with SD-OCT vs. 242.2 ± 81.8 µm (range 97.6 to 459) with SS-OCT (p=0.64; Student's t test paired data). The difference in SFCT and MCT was not statistically significant between both devices, the authors determined. They reported that intraclass correlation coefficient was higher than 0.9 interobserver and interdevice measurements. Furthermore, SFCT Bland-Altman plots showed 95% interobserver measurement agreement within ±34 for SD-OCT, ±22 for SS-OCT and ±60 µm intersystems.

In conclusion, SS-OCT permitted accurate identification of the choroido-scleral border in 100% of normal eyes, suggesting that SS-OCT was the superior modality for the measurement of CT.

SOURCE: Copete S, Flores-Moreno I, Montero JA, et al. Direct comparison of spectral-domain and swept-source OCT in the measurement of choroidal thickness in normal eyes. Br J Opthalmol. 2014;98(3):334–338.

Retinal Vascular Abnormalities in Neovascular AMD

To determine the prevalence of retinal vascular abnormalities (RVA) in neovascular age-related macular degeneration (AMD), a post hoc subanalysis of images acquired during a Phase III randomized controlled trial was undertaken, selecting images from participants with untreated, neovascular AMD in at least one eye.

Protocol-mandated fundus photographs and fluorescein angiograms were acquired at baseline and year two from 107 sham-treated study eyes with neovascular AMD and 107 untreated fellow eyes. Images were reanalyzed by an independent reading center for the presence of RVA, defined as at least one of the following: microaneurysms, vessel staining or leakage, dilated or tortuous vessels, intraretinal hemorrhage, vessel sheathing or narrowing, capillary nonperfusion or capillary infarcts.

The baseline prevalence of RVA in the sham-treated study eyes was 14.4% (15 of 104 gradable images) vs. 8.3% (five of 60) in the fellow eyes with dry AMD. The baseline prevalence of individual RVAs in study eyes was: microaneurysms (6.7%); vessel staining or leakage (6.7%); dilated or tortuous vessels (4.8%); intraretinal hemorrhage (4.8%); vessel sheathing or narrowing (2.9%); capillary nonperfusion (0%); and capillary infarcts (0%). Results were similar at 24 months.

Compared with several studies that relied solely on fundus photographs, this study included fluorescein angiography and found a higher prevalence of RVAs occurring in eyes with neovascular AMD.

SOURCE: Jackson TL, Danis RP, Goldbaum M, et al. Retinal vascular abnormalities in neovascular age-related macular degeneration. Retina. 2014;34(3):568–575.

Use of Once-Daily Low-Dose Doxycycline to Treat Ocular Rosacea

The aim of this retrospective, observational case series was to determine the efficacy of once-daily systemic treatment of ocular rosacea with a slow-release form of 40 mg of doxycycline.

Researchers enrolled 15 patients with ocular rosacea between February 2010 and October 2012. They evaluated patient complaints and clinical findings, including blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, and fluorescein staining of the cornea. They also scored ocular manifestations as follows: 0=absent, 1=mild, 2=moderate and 3=severe. The researchers repeated all measurements at the six-week follow-up visit. They noted that the mean duration of treatment was eight months (range, five to 12 months), and that the mean duration of the follow-up was nine months (range, six to 17 months).

At the baseline visit, 73.3% of the patients had severe complaints, and 80% had severe blepharitis, despite topical therapy with artificial tears and eyelid hygiene. After 12 weeks of systemic therapy, the study researchers noted that severe complaints and blepharitis strongly improved and were seen in only 13.3% and 20% of the patients (p=0.01). They also reported that follow-up investigations six to 17 months after discontinuation of the treatment showed further significant improvement of complaints (absent or mild in 66.7% and 20% of the patients, respectively) and blepharitis (absent or mild in 26.7% and 60% of the patients, respectively). One patient had a mild stomachache so that therapy was shortened to five months.

To conclude, an anti-inflammatory dose of slow-release doxycycline 40 mg given daily may be an effective and safe therapy of ocular rosacea.

SOURCE: Sobolewska B, Doycheva D, Deuter C, et al. Treatment of ocular rosacea with once-daily low-dose doxycycline. Cornea. 2014;33(3):257–260.

  • QLT REPORTS POSITIVE PRELIMINARY RESULTS FROM PHASE Ib RETREATMENT TRIAL OF QLT091001. QLT Inc. announced positive preliminary results from its international, multicenter, open-label Phase Ib clinical trial of repeated treatments of oral QLT091001 in subjects with Leber's congenital amaurosis (LCA) or retinitis pigmentosa (RP) due to inherited genetic mutations in retinal pigment epithelium (RPE65) or lecithin:retinol acyltransferase (LRAT). The proof-of-concept trial was an extension study in which LCA or RP subjects with RPE65 or LRAT mutations who had been previously treated with a single course of QLT091001 in the company's previously completed Phase Ib study, received up to three seven-day courses of QLT091001 to assess visual outcomes and safety following retreatment. Preliminary results of the study show clinically meaningful improvements in visual fields (VF) and visual acuity (VA). To date, 19 of 27 subjects (70%) had an increase in VF retinal area from baseline of ≥ 20% in at least one eye at two consecutive visits within six months from the start of any QLT091001 treatment course. Plus, 70% of subjects had an increase in VA from baseline of five or more letters in at least one eye at two consecutive visits within six months from the start of any treatment course. The final clinical data, including the duration of response and other evaluations, are anticipated for release in the third quarter of 2014.
  • ENROLLMENT BEGINS IN WET AMD STUDY. In 2013, Moorfields and SalutarisMD announced their collaboration to advance the research and development of a novel medical device for use in the treatment of wet age-related macular degeneration (AMD). Now, enrollment has begun in a Salutaris Medical Devices Ltd.-sponsored observational study (“A Prospective Study to Determine Choroidal and Scleral Depth in Subjects with Neovascular Age-related Macular Degeneration Receiving Anti-VEGF Therapy”) conducted at Moorfields Eye Hospital NHS Foundation Trust to accurately measure the scleral and choroid thickness at the fovea and at the choroidal neovascular lesion. The SalutarisMD device employs a minimally invasive retrobulbar episcleral brachytherapy application to the neovascular membranes. The study will use three imaging modalities to determine the depth from the retrobulbar episcleral surface to the vitreous side of the sclera, choroid, and retina at the center of the fovea and choroidal neovascularization. Enrollment of study subjects is ongoing. Read more at www.salutarismd.com.
  • STUDY RESULTS SUPPORT ADDITIONAL MECHANISM OF ACTION FOR LEAD GLAUCOMA DRUG CANDIDATE AR-13324. Aerie Pharmaceuticals Inc. recently announced results of preclinical in vivo research demonstrating the ability of AR-13324 to reduce episcleral venous pressure (EVP) in the eye. The drops previously have been shown to lower intraocular pressure (IOP) by increasing fluid outflow through the trabecular pathway, the eye's primary drain, and by reducing the production of fluid in the eye. The present study affirmed the hypothesis that AR-13324 can also lower IOP through a third mechanism of action, the reduction of EVP, which may represent a breakthrough in the lowering of IOP in patients with glaucoma and ocular hypertension. According to the study results, administration of AR-13324 eye drops once daily demonstrated statistically significant reductions in EVP and IOP in an in vivo model following the third daily dose. EVP decreased by 35% relative to baseline, and IOP was reduced by 39%. Based on these results, the researchers estimated that up to 42% of the reduction in IOP caused by AR-13324 was due to the reduction in EVP. For additional details, click here.
  • FDA GRANTS CLEARANCE FOR VICTUS FEMTOSECOND LASER PLATFORM. Bauch + Lomb's Victus Femtosecond Laser Platform has received 510(k) clearance from the FDA for the creation of cuts/incisions in the cornea of patients undergoing cataract surgery or other ophthalmic treatment requiring cuts/incisions in the cornea. The Victus Femtosecond Laser Platform is designed to support a comprehensive suite of cataract and corneal procedures in a single instrument. This new indication will function in concert with existing advanced proprietary features including an easy-to-use patient interface and real-time OCT imaging to optimize each cataract procedure being performed. Find out more about the Victus Femtosecond Laser Platform at www.victuslaser.com.

  • TOPCON LAUNCHES KR-800S AUTO REFRACTOR WITH SUBJECTIVE TESTING. Topcon Medical Systems has released its KR-800S Auto Kerato-Refractometer with Subjective and Glare Testing. The new five-in-one instrument features the latest in autorefraction technology, incorporating Topcon's Rotary Prism technology for unparalleled accuracy and consistent measurements. It adds on Subjective Visual Acuity testing, allowing you to refine a patient's measurements. The KR-800S features several new tests, including a visual acuity check for near and far distance, a contrast sensitivity test, a grid test and glare testing. It also features a compact and user-friendly design with an 8.5” color touchscreen display that provides quick and accurate readings with minimal training required. For more information, visit www.topconmedical.com.

  • FIRST ANNUAL CURE BLINDNESS VALDEZ CHARITY FUNDRAISER TO TAKE PLACE. ManagementPlus Inc. recently announced its central role as organizer and contributor to the first annual Cure Blindness Valdez charity fundraising event, to be held April 27 through May 3, 2014, in Valdez, Alaska. The event has a fundraising goal of $110,000 and will be led by ManagementPlus chairman Mark Archibald, and hosted by Geoff Tabin, MD, co-founder of the Himalayan Cataract Project. The fundraiser will bring together business leaders, champion skiers and philanthropists for one week of heli-skiing to raise money for construction of a permanent primary eye-care facility in Manang, a village in central Nepal that serves as a central hub for several important land routes.

  • ZEISS PROGRESSIVE CHOICE PLUS SPORT LENSES INTRODUCED. Zeiss has extended its line of Zeiss Progressive Choice lenses with the addition of Zeiss Progressive Choice Plus Sport, a lens specifically designed for wrap frames. According to the company, the Choice Plus Sport design combines advanced customization for the patient's full prescription with proprietary Zeiss prism compensation. This combination widens the area of clear vision by as much as 50% over standard lens designs in wrap frames, while dramatically reducing unwanted prism. The lenses are available in two corridor lengths, with minimum fitting heights of 13mm and 17mm. Zeiss Progressive Choice Plus Sport lenses are fully compatible with i.Scription by Zeiss and are available in 1.50 Hard Resin, 1.53 Trivex and 1.59 polycarbonate, with polarized options in all materials. Additionally, they are available with PhotoFusion by Zeiss and various NXT treatments.

  • OWL HOSTS ANNUAL AWARDS RECEPTION AT ASCRS. Ophthalmic Women Leaders (OWL) will be hosting its annual awards reception honoring influential women within ophthalmology. The reception will be held Monday, April 28 from 5:30 p.m. to 7:00 p.m. during the 2014 American Society of Cataract & Refractive Surgeons Meeting in Boston. Three awards will be presented at the reception: the Vision Woman Award, the Catalyst Award and the Rising Star Award. Nominations will be accepted online through March 14, 2014. OWL members are invited to nominate one or more individuals for each of the awards; nominees are not required to be OWL members. Voting by OWL members for each award will take place from March 19 through April 4, 2014 through www.owlsite.org. Winners will be honored on April 28, 2014 at the annual ASCRS OWL event. Admission to the reception is free for OWL members and $25 for non-members.

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