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FROM THE DESK OF THE EDITOR   YOU MAKE THE DIAGNOSIS   CLINICAL PEARLS   JOURNAL ABSTRACTS   IN THE NEWS   SPONSOR NEWS
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FROM THE DESK OF THE EDITOR

I recently heard that Dave Sattler will be retiring from Alcon after 28 years of service. Dave has been with Alcon in a variety of roles, but many of us, myself included, really got to know Dave after he became the Director of Professional Relations for optometry with Alcon over that last 10 years or so. In that role, Dave worked closely with many optometrists, especially those of us who lecture, and really has served as the face of Optometry for Alcon for many years.

LIVE POLL

What OCT do you currently have? Cirrus Optovue Spectralis Other Don't have one

Dave has always been the most inviting, pleasant person, and seems to have a photographic memory, able to recall hundreds, if not thousands, of ODs names, seemingly instantly. He was one of the first people I met as I started to lecture nationally, and I feel my relationship with him and Alcon really helped make me who I am today. I am honored to consider him a colleague, and dare I say, friend. He has also been a great friend and supporter of the ORS, with us really from the start of our organization many years ago.

I wish him all the best in his future endeavors, and am sure many of the ORS members feel the same. I have heard he will tour the United states in the Oscar Myer Weiner mobile like in the old days, but that might just be a rumor....

Also, please take a look at the very interesting piece by ORS fellow Brad Sutton regarding the role of genetic testing in AMD, as well as its role in determining the optimal vitamin treatment. This is a very hot topic, which I feel will be discussed for some time to come.

Steven Ferrucci, O.D., F.A.A.O.
Editor in Chief

PRESIDENT'S MESSAGE

Joseph J. Pizzimenti, O.D., F.A.A.O.

A Treasure Trove of Knowledge

Larry, Jerry, and Bill. My three predecessors as ORS President. Alexander, Sherman, and Jones, respectively. Each one helped blaze the trail for optometric management of retinal disease. Despite their claims of "slowing down" and rumors of impending retirement (a relative term for these three folks), each one is still providing the rest of us with timely education and sage advice in clinical posterior segment care.

MARCH 2014 POLL RESULTS

The online version of Peripheral Ocular Fundus by ORS Founding President William Jones is available on ScienceDirect.com. For the past two decades, this text has been my go-to source for diagnosis and treatment of disorders of the peripheral retina. The online edition is richly illustrated with full-color images and reader-friendly descriptions of the pathogenesis and treatments for each of the clinical conditions. Bill is still enthusiastically presenting his thought-provoking retina cases, with fantastic images and video, at local and national conferences.

Jerome Sherman has lectured and written extensively on topics ranging from panoramic retinal imaging to the importance of the inner/outer segment photoreceptor junction to visual function. What a dynamo! I have especially enjoyed and benefited from Review of Optometry's Retina Revealed, a web-based, brain-teasing series in which Jerry provides clinicians with the latest technology in retina via online case presentations, as only he can. These 57 (and counting) digital vignettes are available at retinarevealed.com.

Many of us have a well-worn edition of Primary Care of the Posterior Segment within close reach in our offices. Larry Alexander is an original thinker who has stayed at the forefront of retinal care. His latest contribution is truly a labor of love. Eye Lessons is a well-organized, online distribution of information in a logical, evidence-based manner. Of course, "Larry Legend" also provides a bit of entertainment along the way. Try it on your smart phone or tablet by becoming a member (at no charge) at eyelessons.com.

We are fortunate to have these three leaders who continue to promote the advancement of vitreoretinal knowledge for all clinicians!

Warm regards,

Joe
ORS President

YOU MAKE THE DIAGNOSIS

Answer appears later in newsletter.

JOURNAL ABSTRACTS

Three-Year Outcomes of Individualized Ranibizumab Treatment in Patients with Diabetic Macular Edema: The RESTORE Extension Study.

This study was designed to evaluate the long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME). This was a 12-month, multicenter, randomized study and 24-month open-label extension study. In the extension study, patients were selected to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity and disease progression criteria at the investigators' discretion. Laser treatment was also allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser. Outcomes were measured by assessing the change in BCVA as well as any adverse events over 3 years. Overall, 208 patients completed the extension study. In patients treated with ranibizumab during the core study, followed by individualized ranibizumab treatment during the extension study resulted in stabilized BCVA and central retinal thickness at month 12 over the 2-year extension study. In the prior laser group, a progressive BCVA improvement and CRST reduction at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. In conclusion, Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years.

Schmidt-Erfurth U, Lang G, Holz F, et al. Ophthalmology. 121.05 (2014): 1045-1053. print.

Disparity between Visual Fields and Optical Coherence Tomography in Hydroxychloroquine Retinopathy.

American Academy of Ophthalmology recommendations for screening for hydroxychloroquine (HCQ) retinopathy advise ancillary testing such as spectral-domain optical coherence tomography (SD-OCT) and multifocal electroretinography (mfERG) along with visual fields (10-2). However, the relative sensitivity and specificity of screening tests have not been fully resolved. This study characterized a subset of patients with HQC toxicity who show unusual disparity between visual fields and SD-OCT, and therefore, led to questions about the screening practice for patients on this medication.

The study included patients who had used HCQ with greater than 1000 g cumulative dose. There were more than 2000 such individuals, among whom 150 had clear evidence of toxicity. Patients were evaluated by 10-2 visual fields, SD-OCT, and sometimes mfERG or fundus autofluorescence. The findings on visual fields were then compared with that found on SD-OCT.

There were 11 patients among those with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT. None had a history of macular disease or evidence of any other cause of bull's eye maculopathy. On the contrary, all cases with a clear degree of parafoveal damage on SD-OCT showed at least some focal spots of parafoveal field loss. Approximately 10% of patients with early HCQ toxicity showed prominent ring scotomas on field testing without obvious SD-OCT abnormality. This should encourage the inclusion of visual fields as a key screening tool, even when SD-OCT (a more specific and objective test) is also performed. The combination of visual fields and SD-OCT gives both sensitivity and specificity while avoiding unnecessary stoppage of the drug.

Marmor, M. Melles, R. Ophthalmology. 121.06 (2014): 1257-1262. Print.

Intravitreal Aflibercept Injection for Macular Edema Due to Central Retinal Vein Occlusion.
Two-Year Results from the COPERNICUS Study

The purpose of this study was to evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). This was a phase 3, randomized, double masked study. A total of 188 patients with macular edema secondary to CRVO were randomized to receive IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n = 74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (PRN).

The primary efficacy end point was the proportion of patients who gained ≥15 letters in best-corrected visual acuity (BCVA) from baseline to week 24. This study reports week 100 results.

The proportion of patients gaining ≥15 letters was 56.1% versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and 49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively.

The study showed that the visual and anatomic improvements after fixed dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing, with a reduced monitoring frequency from weeks 52 to 100.

Heier JS, Clark WL, Boyer DS, et al. Ophthalmology: Journal of the AAO.

RADIANCE: A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia.

This was a multicenter, 12-month, randomized, double-masked study, constructed to compare the efficacy and safety of ranibizumab versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). The outcome of this comparison was guided by visual acuity stabilization or disease activity criteria. Two-hundred seventy seven patients with visual impairment due to myopic CNV, were randomized to receive ranibizumab on day 1, month 1, and as needed thereafter guided by VA stabilization criteria (group I); ranibizumab on day 1 and as needed thereafter guided by disease activity criteria (group II); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III). Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3. Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6. Improvement in mean BCVA change from baseline to month 12 was greater in groups I and II. At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months.

In conclusion, Ranibizumab treatment provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.

Wolf, S. Vilma, J. Guna, L. et al. Ophthalmology. 120.03 (2014): 682-692. Print.

First Symptoms and their Age of Onset in Macular Telangiectasia Type 2.

A total of 91 patients, with characteristic findings of macular telangiectasia type 2, were interviewed for this study. Their medical charts were reviewed to determine the delay of the correct diagnosis, and subsequent visual function, for 10 years after the onset of first symptoms.

Within the patient cohort, 79% of subjects reported impaired reading ability as their first symptom, followed by metamorphopsia in 12%. The age of onset was most frequent (76%) in the sixth or seventh decade of life and over half (58%) were symptomatic before the age of 60 years. Prior to 2005, the median delay between initial symptoms and the proper diagnosis of macular telangiectasia type 2 was 7 years. Since 2005, advances in retinal imaging have dramatically decreased this diagnostic delay to 1 year. Ten years after the onset of first symptoms, BCVA of the better-seeing eye was ≥20/25 in 35% and ≤20/50 in 17%.

Impaired reading ability was the most common initial visual disturbance of patients with macular telangiectasia type 2. Both clinical knowledge of the disease and utilization of retinal imaging are likely responsible for earlier accurate diagnosis of this unique disease entity.

Heeren TFC, Holz FG, Issa PG. Retina 2014; 34(5): 916-919.

Clinical course of Vitreomacular Adhesion Managed by Initial Observation.

This noncomparative case series investigated the clinical course of patients with idiopathic vitreomacular adhesion (VMA). One hundred and six eyes of 81 patients, mean age 73 years old, were identified as having VMA by spectral-domain optical coherence tomography (OCT) at 3 retina clinics. The VMA was graded based on the OCT findings at both initial and follow-up examinations. Grade 1 was incomplete cortical vitreous separation with attachment at the fovea, Grade 2 was the Grade 1 findings and any intraretinal cysts or clefts, and Grade 3 was the Grade 2 findings and the presence of subretinal fluid. Follow-up continued for 23 months.

At initial evaluation, forty-three eyes (41%) were classified as Grade 1 VMA, 56 eyes (52%) as Grade 2, and 7 eyes (7%) as Grade 3. By the last follow-up, spontaneous release of VMA occurred in 34 eyes (32%) and pars plana vitrectomy was performed in a total of 5 eyes (4.7%). Mean BCVA was 20/37 at baseline (range, 20/20-20/200) and 20/35 at the last examination (range, 20/20-20/400).

In this patient cohort with mild symptoms, the clinical course of patients with VMA managed by initial observation was favorable.

Vishak J, Flynn HW, Smiddy WE, et al. Retina 2014; 34(3): 442-446.

Retinal Measurements For Diagnosis of Parkinson Disease.

The purpose of this investigation was to explore the diagnostic ability of SD-OCT for the detection of Parkinson disease. Retinal nerve fiber layer (RNFL) and retinal thickness parameters, from Spectralis SD-OCT, were collected in patients with Parkinson disease (n = 111) and healthy subjects (n = 200). Linear discriminant functions (LDFs) were developed, based on RNFL parameters and retinal thickness, and a validating set was utilized. Receiver operating characteristic curves were plotted and compared with the standard parameters provided by OCT. Sensitivity and specificity were then used to evaluate diagnostic performance.

The Retinal LDF, based on retinal thickness parameters, yielded the highest sensitivity and provided the best performance: 31.173 + 0.026 × temporal outer - 0.267 × superior outer + 0.159 × nasal outer - 0.197 × inferior outer - 0.060 × superior inner + 0.049 × foveal thickness. The largest areas under the receiver operating characteristic curve were 0.902 for Retinal LDF. Measurements of retinal thickness varied between healthy subjects and those with advanced Parkinson disease. Further investigation is necessary to identify clinical applicability.

Garcia-Martin E, Satue M, Otin S, et al. Retina 2014; 34(5): 971-980.

A Randomized Trial to Assess Functional and Structural Effects of Ranibizumab versus Laser in Diabetic Macular Edema (the LUCIDATE Study).

This prospective, randomized study sought to compare the functional and structural effects of ranibizumab versus macular laser therapy in patients with center-involving diabetic macular edema. During a 48-week period, 33 eyes with center-involving diabetic macular edema were randomized 2:1 to 3 loading doses of ranibizumab then retreatment every 4 weeks as needed; or macular laser therapy at baseline, repeated as needed every 12 weeks. Structural imaging studies looked specifically at linear dimension and area of foveal avascular zone, perifoveal capillary dropout grade, and presence of morphologic features of diabetic macular edema. Visual acuity, retinal sensitivity, color contrast, thresholds, pattern and full-field electroretinogram amplitudes and implicit times, and multifocal electroretinogram amplitude distribution were measured and were reported at 12, 24, and 48 weeks.

Ranibizumab-treated subjects gained 6.0 vs. 0.9 letters lost for laser, demonstrated increased color contrast thresholds, and improved retinal sensitivity including improved electrophysiologic function. Better retinal thickness reduction and structural improvement were also seen with ranibizumab therapy than in the laser group. There was no evidence of progressive ischemia with ranibizumab therapy.

Thus, this study concluded that ranibizumab therapy for the treatment of diabetic macular edema seems to improve retinal function and structure in addition to visual acuity and color contrast.

Comyn O, Sivaprasad S, Peto T, et al. American Journal of Ophthalmology. 2014;157(5):960-970.

Intra-arterial Chemotherapy for Retinoblastoma in 70 Eyes Outcomes Based on the International Classification of Retinoblastoma.

In this study, investigators analyzed their 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy. A total of 70 eyes of 67 patients were reviewed. Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary.

The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1–7 sessions).

With a mean follow up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death.

Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.

Shields CL, Maniandavida FP, Lally SE et al. Ophthalmology: Journal of the AAO Volume 121, Issue 7, Pages 1453–1460, July 2014.

Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial.

The purpose of this study was to demonstrate the safety and efficacy of the gene therapy vector to be used in a proposed gene therapy clinical trial for the treatment of Leber Hereditary Optic neuropathy (LHON).

Most patients with LHON, a degenerative visual disorder have the G11778A mutation, which involves ND4 gene. In the laboratory setting, mitochondrial ND4 subunit of complex I was modified in the nuclear genetic code for import into mitochondria and was directed into the organelle by using a targeting sequence of allotropic expression.

The modified gene was packaged into adeno-associated viral vectors and injected intra-vitreally into a rodent eyes as well as in ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis.

Follow ups included fundus photography, OCT and multifocal or pattern electroretinography. The final outcome was to measure expression of human ND4 gene as well as rescue of vision loss and optic neuropathy in the rodent eyes that were injected with a mutant G11778A ND4 homologue responsible for most cases of LHON.

By one week, the human ND4 was expressed in almost all mouse retinal ganglion cells after injection and ND4 integrated into the mouse complex I. In rodent eyes that were also injected with a mutant allotopic ND4, wild-type allotropic ND4 prevented defective adenosine triphosphate synthesis, decreased apoptosis of retinal ganglion cells, reduced visual loss and prevented the axon death in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression within most retinal ganglion cells and within a 3 month follow period, these eyes experienced no serious adverse reactions.

In conclusion, this study demonstrated the expression of the allotopic ND4 vector in the ex vivo human eye, the safety of the test article and the rescue of the LHON mouse model supports the need for further clinical testing.

Koilkonda R, Yu H, Chou T et al., Jama Ophthalmology 2014; 132(4) p 409-420.

Effect of Doxycycline vs. Placebo on Retinal function and Diabetic Retinopathy Progression in Patients with Severe Nonproliferative or Non-High Risk Proliferative Diabetic Retinopathy.

The purpose of this proof-of-concept study was to determine whether low-dose oral doxycycline monohydrate slows the deterioration of or improves retinal function and whether it can slow the progression of or result in regression of diabetic retinopathy (DR) in patients with severe non proliferative diabetic retinopathy (NPDR) or non-high-risk proliferative (PDR).

Thirty patients with one or more eyes diagnosed with severe NPDR or non high risk PDR were enrolled in this randomized, double-masked, 24 month clinical trial. Half the participants were randomized into either a placebo group or into a doxycycline group where patients received 50mg of doxycycline daily for 24 months.

Visual outcome was measured with frequency doubling perimetry (FDP), Humphrey photopic Sita 24-2 visual fields, contrast sensitivity, dark adaptation, visual acuity, quality of life and clinical measures of retinal and macular thickening, macular volume and retinal vessel diameters in accordance with the Early Treatment Diabetic Retinopathy Study.

The study found that the mean FDP foveal sensitivity decreased in the placebo group (-1.9 dB) after 24 months whereas it increased in the doxycycline group (+1.8dB), as early as 6 months and continued to improve over the course of the study. In the other visual function outcome measures however, there was no difference between the placebo and treated group.

In conclusion, there may be a link between oral anti-inflammatory agents such as doxycycline and subclinical improvement in inner retinal function, which in this study was measured by FDP. Oral doxycycline may be a promising therapeutic drug in targeting the inflammatory component of DR.

Scott I, Jackson G, Quillen D, et al. Jama Ophthalmology 2014; 132(5) p535-543 Volume 121, Issue 7, Pages 1414–1420.e1, July 2014.

IN THE NEWS

	Insignificant Link Found Between Genotype, Response To AREDS Supplements Genotype had an insignificant association with response to nutritional supplementation, according to study findings published in Ophthalmology. In a retrospective analysis of data from the first AREDS, researchers attempted to gauge whether genotypes at two major loci related to age-related macular degeneration—complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2)—had any significant effect on the relative benefits of AREDS supplements in a subset of patients at high risk for progression to late AMD. Patients were randomly assigned to one of four AREDS supplement treatment arms: placebo; vitamins C and E, and beta-carotene; zinc or antioxidant plus zinc. Among the 1,237 patients analyzed, late AMD developed in 385 patients (31.1%). The CFH and ARMS2 genotypes were associated independently with development of late AMD (P = .005 and P < .0001, respectively). Results showed that the combination of CFH, ARMS2 and treatment with the four different AREDS components produced no statistically significant interaction, according to the researchers.
	Eylea Shows Sustained Improvements In BCVA Vs. Laser Photocoagulation Data from the phase 3 VIVID-DME trial indicate that aflibercept injection provided sustained improvements in best corrected visual acuity from baseline at 2 years compared with laser photocoagulation in patients with diabetic macular edema. Patients in the VIVID-DME trial were randomly assigned to either aflibercept (Eylea, Regeneron) 2 mg monthly, aflibercept 2 mg every 2 months or the comparator treatment of laser photocoagulation. In patients who received aflibercept 2 mg monthly, 2-year data indicated a mean change in BCVA from baseline of 11.4 letters (10.5 letters at 52 weeks, P < .0001 vs. laser), according to a company press release. Patients assigned to aflibercept 2 mg every 2 months had a mean change in BCVA from baseline of 9.4 letters (10.7 letters at 52 weeks, P < .0001 vs. laser). The most common adverse events included conjunctival hemorrhage, cataract and increased IOP, according to the release. Full 2-year data from the VIVID-DME trial will be presented at an upcoming scientific conference, according to the release.
	HARBOR Study: Visual, Anatomic Improvements Maintained At 2 Years Ranibizumab improved vision for 2 years in patients with subfoveal neovascular age-related macular degeneration, according to results of the HARBOR study, published in Ophthalmology. The randomized, controlled, multicenter phase 2 study included 1,098 patients 50 years and older with treatment-naïve subfoveal wet AMD. Patients were randomly assigned to one of four groups: 0.5 mg monthly injections (group one), 0.5 mg as needed (group two), 2 mg monthly (group three) or 2 mg as needed (group four). Outcome measures included mean change in best corrected visual acuity from baseline at 12 and 24 months, percentage of patients who gained 15 or more letters of BCVA, mean number of injections and mean change in central foveal thickness from baseline. Mean number of injections through 24 months was 21.4 in group one, 13.3 in group two, 21.6 in group three and 11.2 in group four. The second group required a mean 5.6 injections and the fourth group required 4.3 injections at 24 months, according to the researchers. At 24 months, mean gain in BCVA from baseline was 9.1 letters in group one, 7.9 letters in group two, eight lines in group three and 7.6 lines in group four. The percentage of patients who gained at least 15 letters was 34.5% in the first group, 33.1% in the second group, 37.6% in the third group and 34.8% in the fourth group. Snellen equivalent visual acuity was 20/40 or better in 44% to 52% of patients at 12 months and in 45% to 50% at 24 months, according to the researchers.
	Ciliary Neurotrophic Factor Yields Macular Thickness Change In Eyes With Retinitis Pigmentosa Change in macular thickness was identified as a dose-dependent response to a ciliary neurotrophic factor implant in eyes with retinitis pigmentosa, according to a study in Retina. Data were culled from the phase 2 Ciliary Neurotrophic Factor (CNTF)-3 and CNTF-4 clinical trials. Study investigators analyzed five patients from the CNTF-3 trial and three patients from the CNTF-4 trial. Mean patient age was 50 years. Two patients from the CNTF-3 study received a low-dose CNTF implant (250 ng per million cells per 24 hours). Three patients from the CNTF-3 trial and all three patients in the CNTF-4 trial received a high-dose implant (800 ng per million cells per 24 hours). Fourier-domain optical coherence tomography (FD-OCT) was used to evaluate macular thickness. FD-OCT imaging was undertaken preoperatively and up to 30 months after implantation to assess macular thickness. A 3% change in mean macular thickness was the benchmark for measurable change. Among three patients in the CNTF-3 cohort who received a low-dose implant, mean change in mean macular thickness from baseline to 18 months was -4.47 µm to 6 µm. Among the three patients in the CNTF-3 group who received a high-dose implant, mean macular thickness increased by 19.25 µm in one eye at 18 months. In the CNTF-4 group, mean macular thickness increased by 27.08 µm in one eye and by 31.36 µm in the fellow eye at 30 months. "Amongst these three responsive high-dose implant eyes, overall thickening of the retina could not be attributed to any specific retinal layer," the authors wrote.
	Centervue Receives 510(K) Clearance For Redesigned Macular Integrity Assessment The U.S. Food and Drug Administration has granted CenterVue 510(k) clearance for its next-generation Macular Integrity Assessment device, according to a company press release. The Macular Integrity Assessment (MAIA) for scanning laser ophthalmoscopy confocal microperimetry now features a more ergonomic design and smaller footprint, as well as a more powerful PC, according to the release. Additionally, the redesign allows for faster examinations and includes automatic alignment and dynamic multifixation. "FDA clearance of the MAIA represents significant opportunity for eye care professionals. Through the device's combined structure-function analysis, this device is an essential tool for a variety of retinal diseases," CenterVue CEO Cliff Wright, OD, said in the press release. "From diagnosis, to monitoring progression of both retinal pathologies, and treatment efficacy, the MAIA is the first easy-to-use Microperimetry and represents a significant advance in macular functional analysis."
	No Positive Association Found Between AMD And Alzheimer's Disease, Dementia No positive association was found between age-related macular degeneration and Alzheimer's disease or dementia, according to a study in JAMA Ophthalmology. Researchers examined English National Health Service hospital episode statistics from Jan. 1, 1999, to Feb. 28, 2011, which comprised 65,894 patients with AMD and 168,092 patients with dementia; more than 7.7 million people were in a reference cohort. Subjects were analyzed for risk of Alzheimer's disease or dementia after diagnosis of AMD and risk of AMD after diagnosis of Alzheimer's disease or dementia. No elevated risk of Alzheimer's disease or dementia after AMD was reported, and there was a low likelihood of being of being admitted to the hospital with AMD after Alzheimer’s disease or dementia. The study authors also found that subjects with dementia in England were less likely to receive treatment for AMD. "Further research across a variety of countries is required to determine whether people with dementia are receiving appropriate investigation and treatment for AMD, as well as identify and address any potential barriers," they said.
	Eylea Recommended For Approval In Europe For DME Visual Impairment Aflibercept injection has been recommended for approval by the European Committee for Medicinal Products for Human Use for the treatment of visual impairment due to diabetic macular edema, according to a Regeneron press release. The recommendation is based on positive data from the phase 3 VIVID-DME and VISTA-DME studies. "Diabetes is a growing health concern worldwide, and this milestone brings us one step closer to being able to offer patients and physicians in the European Union a new therapeutic option for the treatment of diabetic macular edema," George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Laboratories, said in the press release. Two-year data from the VIVID-DME trial are expected later in 2014. Aflibercept (Eylea) was approved in the United States for the treatment of wet age-related macular degeneration in November 2011 and for macular edema following central retinal vein occlusion (CRVO) in September 2012. It has also been approved in the European Union and in other countries for the treatment of wet AMD and macular edema following CRVO, according to the release. The European Commission’s final decision is expected in the second half of 2014.
	Nicox Launches Retnagene Test Portfolio Nationwide Nicox Inc. announced the national brand launch of RetnaGene tests in the U.S., according to an announcement from Nicox S.A. and Sequenom Inc. As detailed in a press release, the RetnaGene test portfolio includes RetnaGene AMD and RetnaGene LR, which evaluate age-related macular degeneration risk. "Expanding access to the RetnaGene portfolio of tests is an important milestone in the progress of the Nicox Ophthalmic Diagnostics franchise in the U.S.," Jerry St. Peter, executive vice president and general manager of Nicox Inc., said in the release. "AMD is a leading cause of blindness in the U.S. and is estimated to affect over 15 million Americans, including 10% to 15% suffering from an advanced form of the disease." "The RetnaGene tests allow for improved patient management, by examining the most relevant genetic markers for a more accurate prediction of advanced AMD risk," St. Peter continued. "Both the RetnaGene tests and our groundbreaking test for the early detection of Sjögren's syndrome, Sjö, will be supported by our rapidly expanding specialist sales force." "We are pleased with the timely progress of our partnership with Nicox and we are confident in Nicox's ability to successfully expand access to the RetnaGene portfolio of tests in the ophthalmic arena in the U.S.," William Welch, CEO of Sequenom Inc., said in the release. Sequenom Laboratories granted Nicox Inc. promotion and marketing rights for the tests in January.
	Regeneron Seeks Marketing Clearance In EU For Eylea Injection In BRVO Regeneron Pharmaceuticals and Bayer HealthCare have applied to the European Medicines Agency to obtain marketing authorization in the European Union for Eylea in the treatment of macular edema associated with branch retinal vein occlusion, according to a press release. The application is based on the VIBRANT trial, a phase 3 controlled, randomized study of patients with macular edema following BRVO. Results showed that 53% of patients who received monthly Eylea (aflibercept) 2 mg injections gained 15 letters, or three lines, of best corrected visual acuity from baseline to 24 weeks, compared with 27% of patients who underwent standard laser treatment (P < .001). Patients who received aflibercept injections gained a mean 17 letters of BCVA over baseline; patients who underwent laser treatment gained a mean 6.9 letters (P < .0001). Aflibercept was also well-tolerated; at 24 weeks, the most common adverse events were conjunctival hemorrhage and ocular pain. The incidence of serious adverse events was 9.9% in the aflibercept group and 9.8% in the control group. No cases of intraocular inflammation were reported. The U.S. Food and Drug Administration approved aflibercept for neovascular age-related macular degeneration in November 2011 and for macular edema associated with central retinal vein occlusion in September 2012. The drug is approved in the EU and other regions for wet AMD and macular edema associated with CRVO, the release said. Regulatory submissions for aflibercept have also been made in the U.S. for treatment of macular edema associated with BRVO, and in the U.S. and EU for treatment of diabetic macular edema, according to the release.
	Ophthotech, Novartis Enter Into Ex-US Licensing And Commercialization Agreement Ophthotech Corp. has entered into an ex-U.S. licensing and commercialization agreement with Novartis Pharmaceuticals for Fovista, an anti-PDGF in development for the treatment of wet age-related macular degeneration, according to a press release. This agreement entitles Novartis to commercialize Fovista in markets outside of the United States. Ophthotech will continue to commercialize Fovista in the United States and lead the Fovista phase 3 wet AMD clinical program. "This agreement represents an important achievement for the company as we continue to execute on a strategy to deliver science-driven retinal products and offer physicians multiple treatment options to improve patient outcome," David R. Guyer, MD, Ophthotech chief executive officer and chairman of the board, said in the release. Under this agreement, Ophthotech could receive more than $1 billion in upfront and milestone payments, excluding future royalties. The company could also potentially receive up to $330 million in immediate payment, upfront fee and near-term milestones, as well as $300 million in contingent future ex-U.S. marketing approval milestones, $400 million in ex-U.S. sales milestones, and royalties on ex-U.S. sales, the release said.
	Repeat-Use Procedure For Iluvien Receives Positive Outcome In 10 European Countries Alimera Sciences has announced a positive outcome for its repeat-use procedure for Illuvien, a treatment for diabetic macular edema, in an additional 10 European countries, according to a company press release. As part of the regulatory process, the company will now enter a national phase to obtain marketing authorization from each of the 10 countries, which include Ireland, the Netherlands, Belgium, Luxembourg, Sweden, Denmark, Finland, Norway, Poland and the Czech Republic. Iluvien will be indicated for the treatment of vision impairment associated with chronic DME, according to the release. "Achieving a favorable outcome for Iluvien in these additional EU countries is a significant milestone for Alimera and very encouraging for the many patients throughout Europe with this devastating disease," Dan Myers, president and CEO of Alimera, said in the press release. "We will continue to work closely with these countries during the national phase to obtain Iluvien marketing authorization in each one."

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