Volume 14, Number 1
Monday, January 6, 2014


In this issue: (click heading to view article)
######### Progressive Neuroretinal Rim Loss as a Surrogate Endpoint for Development of VF Loss in Glaucoma

######### Clinical Outcomes Following Switch from Intravitreal Ranibizumab to Aflibercept in Neovascular AMD

######### Change in Drusen Volume Used as Endpoint for the Study of Complement Inhibition in AMD
######### OCT Predicts Visual Outcome in Acute CRVO
######### Briefly

Progressive Neuroretinal Rim Loss as a Surrogate Endpoint for Development of VF Loss in Glaucoma

To evaluate the validity of using progressive loss of neuroretinal rim area as a surrogate endpoint for the development of visual field loss in glaucoma, this prospective, observational cohort study included 492 eyes of 328 patients classified with suspected glaucoma at the baseline visit.

These eyes had an average of 7.4 ± 2.8 confocal scanning laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6 ± 1.6 years. Rim area measurements were acquired with CSLO during follow-up. The visual field endpoint was considered the development of three consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect (PTE) are requisites for a suitable surrogate end point. A joint longitudinal survival model was used to evaluate the ability of rates of rim area loss in predicting visual field development, adjusting for confounding variables (baseline age, race and corneal thickness and follow-up measurements of intraocular pressure [IOP] and pattern standard deviation). The PTE was calculated by comparing the effect of IOP on the risk of development of visual field loss when incorporating rim area loss in the same model with the effect of IOP in the model excluding rim area measurements. The main outcome measure was predictive strength, measured by survival-adapted R² and PTE.

It was reported that 62 of 492 eyes (13%) developed visual field loss during follow-up. It was also noted that the mean rate of rim area change in eyes that developed visual field loss was –0.011 mm²/year versus –0.003 mm²/year in eyes that did not (p<0.001). In the multivariable model, each 0.01 mm²/year faster rate of rim area loss was associated with a 2.94 higher risk of visual field loss (hazard ratio, 2.94; 95% confidence interval, 1.38 to 6.23; p=0.005). R² values were 62% and 81% for univariable and multivariable models, respectively. The PTE was 65%.

Progressive rim area loss was highly predictive of the development of visual field loss in glaucoma and explained a significant PTE on the clinically relevant outcome. These findings suggest that rim area measurements may be suitable surrogate endpoints in glaucoma clinical trials.

SOURCE: Medeiros FA, Lisboa R, Zangwill LM, et al. Evaluation of progressive neuroretinal rim loss as a surrogate end point for development of visual field loss in glaucoma. Ophthalmology. 2014;121(1):100–109.

Clinical Outcomes Following Switch from Intravitreal Ranibizumab to Aflibercept in Neovascular AMD

Researchers sought to describe the treatment response to aflibercept in patients who have exudative age-related macular degeneration (AMD) that showed insufficient or diminishing treatment effects under ranibizumab.

From December 2012 till June 2013, they collected the information of all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab in a database and reviewed them retrospectively. They analyzed clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans for the time frame before, during and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment.

According to the researchers, 71 eyes of 65 patients were included in the study. They reported that all eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range three to 43). For the total group, the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR, the study researchers noted. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 µm to 349.52 µm under ranibizumab treatment and from 338.76 µm to 272.00 µm under aflibercept treatment. Interestingly, 33% of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment.

To conclude, aflibercept appears to be an effective choice for patients with neovascular AMD who were resistant to previous therapy of ranibizumab. However, the longevity of this effect still remains questionable.
SOURCE: Heussen FM, Shao Q, Ouyang Y, et al. Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2013; December. [Epub ahead of print].

Change in Drusen Volume Used as Endpoint for the Study of Complement Inhibition in AMD

The authors of the following single-center, prospective, randomized, double-masked clinical trial aimed to evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component five. They randomized patients 2:1 to receive intravenous eculizumab or placebo over 26 weeks. Decrease in drusen volume of at least 50% at 26-week follow-up was the main outcome measure

Mean drusen cube root volumes were 0.49 mm and 0.47 mm (p=0.64) at baseline and 0.51 mm and 0.42 mm (p=0.17) at 26 weeks in the eculizumab and placebo groups, respectively. In the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks.

Systemic complement inhibition with eculizumab did not significantly reduce drusen volume, the study authors concluded. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment's ability to prevent drusen growth, neovascularization, and the formation of geographic atrophy over one year.

SOURCE: Filho CA, Yehoshua Z, Gregori G, et al. Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. OSLIRetina. 2013; Dec 19. [Epub ahead of print].

OCT Predicts Visual Outcome in Acute CRVO

Investigators retrospectively reviewed 50 consecutive eyes with acute central retinal vein occlusion (CRVO) of less than one month of symptom duration before presentation to examine the clinical features of CRVO in relation to the presence of a prominent middle limiting membrane (p-MLM) sign on presenting optical coherence tomography (OCT), which may suggest macular ischemia and poor visual outcome.

They used a hyperreflective line located in the outer plexiform layer (p-MLM) in OCT as a sign of acute ischemia. The investigators grouped cases with p-MLM and compared them with the group of eyes with no p-MLM sign (non-MLM group) for clinical features including visual acuities, central fovea thickness and CRVO types.

Among the 50 eyes, 14 (28%) eyes showed a p-MLM sign, 21 (42%) eyes did not, and others had equivocal findings. The study investigators reported that eyes with p-MLM sign presented worse initial and final best-corrected visual acuity (BCVA) compared with the non-MLM group (1.10 ± 0.72 vs. 0.47 ± 0.49 logMAR in the initial BCVA, p=0.007; and 1.08 ± 0.86 vs. 0.32 ± 0.41 logMAR in the final BCVA, p=0.044) in patients with a follow-up duration of six months or longer. They also found that p-MLM group eyes showed a higher tendency toward being classified as ischemic type CRVO (57.1 vs. 4.8%, p=0.001).

In conclusion, CRVO showing p-MLM on OCT had worse visual outcome with higher incidence of being classified into ischemic type CRVO.

SOURCE: Ko J, Kwon OW, Byeon SH. Optical coherence tomography predicts visual outcome in acute central retinal vein occlusion. Retina. 2013; Dec 27. [Epub ahead of print].

  • OPHTHALIX ANNOUNCES TOP-LINE RESULTS OF PHASE III STUDY WITH CF101 FOR DRY-EYE SYNDROME. OphthaliX Inc. released results from a 24-week, placebo-controlled Phase III study involving 237 patients with moderate to severe dry-eye syndrome who were treated with its licensed drug CF101, an A3 adenosine receptor agonist. In the study, patients were randomized to receive two oral doses of CF101 (0.1 mg or 1.0 mg) or a placebo, for 24 weeks. While CF101 did not meet the primary efficacy endpoint of complete clearing of corneal staining, or the secondary efficacy endpoints, the drug was found to be well-tolerated. The company will conduct a retrospective analysis of the Phase III dry-eye syndrome study data to determine whether there is a correlation between the CF101 target, the A3 adenosine receptor, expression and patients' response to the drug. This analysis is based on recent positive data from a Phase IIb rheumatoid arthritis study of CF101. OphthaliX is also developing CF101 for the treatment of glaucoma and uveitis. Interim data from the ongoing Phase II study in glaucoma is expected to be released in 2014. Learn more here.
  • OPHTACATH RECEIVES FDA APPROVAL. According to FCI Ophthalmics Inc., the FDA has approved its OphtaCath lacrimal duct balloon catheter, which achieves true dilation of the lacrimal duct and rapidly and effectively treats the symptoms of epiphora. The company says OphtaCath is a less-invasive alternative to incisional procedures such as dacryocystorhinostomy and eliminates the placement of tubes, resulting in less trauma. OphtaCath comes packaged sterile in 2-mm or 3-mm kits with one or two balloon catheters and a highly precise and easy-to-use disposable inflation device. Additionally, the catheter's tapered tip and low profile allow for easy insertion and removal of the balloon catheter. Now approved for sale in the United States, OphtaCath is available only from FCI Ophthalmics Inc. Call (800) 932-4202 or email info@fci-ophthalmics.com.
  • INTRODUCTORY OFFERS SUPPORT THE LAUNCH OF LASH ADVANCE. MediNiche Inc. has two special eye-care professional (ECP) offers to support the launch of its new Lash Advance non-prescription lash and brow gel. The offers are intended to give ECPs the option to TRY IT! or BUY IT! In lieu of samples, the first offer provides ECPs and their staff with an opportunity to try new Lash Advance for just $10 plus shipping and handling (80% off the regular retail price). The Eyecare Professional Courtesy Pricing Offer can be accessed by visiting www.mediniche.com/LAprofessionalpricing.html or by calling (888) 325-2395. The second offer is the Introductory Purchase Offer, which runs until March 31, 2014. ECPs and optical dispensaries can purchase one dozen packages of Lash Advance at the regular wholesale price of $24/package and receive a 25% discount, two free packages, free shipping, a free counter display, patient/staff materials and reorder privileges through the end of 2014. Visit www.mediniche.com/lashadvanceoffer.html or call (888) 325-2395.

  • DR. DAVID GUYER APPOINTED TO THROMBOGENICS BOARD OF DIRECTORS. ThromboGenics NV has announced the appointment of Dr. David Guyer to its board of directors. Dr. Guyer is a long-standing member of the U.S. retina community and is currently the co-founder and chief executive officer of Ophthotech Corp. Additionally, he serves as chairman of its board of directors and he also co-founded and served as CEO and director of Eyetech Pharmaceuticals, Inc. Click here to read more about Dr. Guyer.


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