Inside This Issue 

CLINICAL PEARLS

ANSWER TO "YOU MAKE THE DIAGNOSIS"

This OCT represents a case of Acute macular neuroretinopathy (AMNR). The OCT reveals disruption at the IS/OS junction. The FFA is unremarkable.

AMNR is a rare condition that occurs in healthy, young women and may result in transient or permanent vision loss. The condition was first described in 1975 by Bos and Deutman, who believed that the lesions involved the inner retina and the superficial retinal layers. The condition may be associated with the use of oral contraceptives or with a recent febrile illness. Ophthalmoscopically, these patients will present with lobular, reddish brown, wedge-shaped lesions in the macular region. Resolution of the lesions has been reported, however the lesions may persist for up to nine years.

The pathophysiology of this condition is unclear and there is no treatment. Eighty-three percent of cases affect younger women, nearly half of who report an associated viral illness. Other reported associations include oral contraceptive use and the intravenous administration of epinephrine, after intravenous contrast agents and after bodily trauma. AMNR has also been associated with heavy caffeine consumption. The association of this condition with oral contraceptive use and intravenous sympathomimetic administration suggests a vascular etiology, although angiography has failed to demonstrate a perfusion defect.

Close inspection of the OCT shows that the abnormality occurs in the outer retina, with disruption at the IS/OS junction (inner segment/outer segment junction). Close observation of the outer retina reveals a focal signal reduction. As a result, the photoreceptor outer segments are affected resulting in irregularity at the IS/OS junction. The thin line above the high signal bands of the outer retina, corresponding to the external limiting membrane are intact. The OCT further demonstrates that the structural changes in the outer retina may be reversible in patients with AMNR as can be visualized via serial observation of the OCTs as the retina is healing.

Julie Rodman, O.D., F.A.A.O.,
ORS Fellow

GALILEO Results Show Visual Acuity Gains Diminished With Less Frequent Monitoring

Visual improvements gained during the fixed dosing period of intravitreal aflibercept injection in the GALILEO trial were not sustained once an as-needed dosing regimen was implemented with reduced monitoring frequency, according to 18-month results presented at the Association for Research in Vision and Ophthalmology meeting.

Treatment with fixed monthly Eylea (aflibercept, Regeneron) over 24 weeks resulted in rapid and sustained gains in visual acuity, and those gains were largely maintained with monthly monitoring and less frequent as-needed dosing during weeks 24 to 52, Ogura said. However, the visual acuity gains were reduced with as-needed dosing and infrequent monitoring — every 8 weeks — during weeks 52 to 76.

The double-masked phase 3 trial randomized 106 patients with macular edema secondary to central retinal vein occlusion to receive intravitreal aflibercept 2 mg every 4 weeks for 24 weeks and 71 patients to receive sham injection every 4 weeks. From weeks 24 to 52, aflibercept patients were evaluated monthly and given injections as needed. Patients in the sham arm continued to receive monthly injections. From weeks 52 to 76, all patients were evaluated every 8 weeks and put on an as-needed regimen.

GEFAL Results Support CATT Findings

Like the CATT trial, the French Evaluation Group Avastin Versus Lucentis found also that bevacizumab is non-inferior to ranibizumab, the GEFAL investigators reported at the Association for Research in Vision and Ophthalmology meeting.

"We found that, for our primary outcome, which is visual acuity, bevacizumab is non-inferior to ranibizumab," study author Laurent Kodjikian, MD, PhD, said in a press briefing. The mean visual acuity difference between the two drugs was 1.89 letters, which is clinically meaningless, Kodjikian said.

In the double-masked, randomized, interventional GEFAL trial, 255 patients received 1.25 mg Avastin (bevacizumab, Genentech) and 246 patients received 0.5 mg Lucentis (ranibizumab, Genentech). All patients received monthly injections for the first 3 months and were assessed for treatment thereafter. A mean of seven injections was necessary per patient within the year for both drugs.

Both drugs resulted in rapid and substantial decrease in thickness and fluid, although neither drug eliminated fluid in all eyes.

There were no differences between the two drugs regarding safety, but too few patients were enrolled for too short a period to make a comment on safety of the drugs, Kodjikian said. More systemic serious adverse events were reported with bevacizumab, but individual data regarding each event is needed before a conclusion can be drawn, he said.

Novel VEGFR/PDGFR Inhibitor Well-Tolerated In Treatment Of Wet AMD

A new treatment for neovascular age-related macular degeneration was well-tolerated and showed potential efficacy, according to a news release.

At the Association for Research in Vision and Ophthalmology meeting, Xcovery Vision released preliminary data from a phase 1/2 clinical trial of the VEGFR/PDGFR inhibitor X-82.

"The data show that 50 mg of X-82 once daily achieves exposures well above the concentration required to inhibit new blood vessel formation, which suggests that the dose should be well-tolerated and could be efficacious in treating wet AMD patients," Chris Liang, PhD, executive vice president and chief scientific officer of Xcovery Vision, said in the release.

X-82 is a tyrosine kinase inhibitor in an oral formulation that blocks pathologic blood vessel growth and targets forms of neovascularization in ophthalmic settings, such as AMD and diabetic retinopathy, the release said.

Patient enrollment in the study began at five centers around the U.S. in November 2012.

According to ClinicalTrials.gov, the trial includes patients aged 50 years or older with active choroidal neovascularization associated with AMD, subretinal hemorrhage less than 50% of total lesion size, and best corrected visual acuity of 20/40 to 20/200 or 20/320 in the study eye and equal or better BCVA in the fellow eye. Patients who received previous anti-VEGF treatment, photodynamic therapy, external beam radiation, subfoveal focal laser photocoagulation, submacular surgery or transpupillary thermotherapy in the study eye are excluded.

Nonpenetrating Brachytherapy Device Shows Positive Early Safety, Efficacy Results

A new brachytherapy approach has been shown to increase best corrected visual acuity and was well-tolerated in a small group of patients with age-related macular degeneration, according to a poster presentation at the Association for Research in Vision and Ophthalmology meeting

Kamaljit S. Balaggan, MBBS, and colleagues presented a poster on the early results with the SMD-1 novel episcleral brachytherapy device developed by SalutarisMD. The class 1 medical device delivers 24 Gy of radiation for 5.5 minutes to the macula through a probe placed adjacent to the macular sclera via a sub-Tenon retrobulbar approach, according to the authors. The six patients treated in this study also received anti-VEGF injections.

The probe consists of a stainless steel cannula that is 1.8 mm in diameter.

The procedure was well-tolerated, and no serious adverse effects were reported, according to the authors. All patients experienced an increase in BCVA at 3 months, with a mean gain of 19 letters.

By 12 months, three patients maintained or improved BCVA, and three patients experienced a loss of BCVA. Two patients needed no further anti-VEGF injections at follow-up. All patients showed a reduction in macular thickness compared with baseline.

Higher Success With Ocriplasmin For Vitreomacular Traction Found In Certain Population Groups

When considering using ocriplasmin for vitreomacular traction, the most important consideration is the size of the macular traction, but age, presence of epiretinal membrane and whether the eye is phakic also need to be taken into account, according to a speaker Peter K. Kaiser, MD, at the Cole Eye Institute Retina Summit at held before the. Association for Research in Vision and Ophthalmology meeting,

"If epiretinal membrane is present, that is not a good sign. Phakic eyes are more likely to have release as well as in patients younger than 65," he said.

Kaiser said good candidates for Jetrea (ocriplasmin, ThromboGenics) have a vitreomacular adhesion of less than 1,500 µm.

"If someone is over 65, I would not say to not have it. It worked in all age groups, but it worked better in younger patients. It works for older patients, just not as well," he said.

TNF Inhibitor Effective In Patients With Severe Uveitis

Adalimumab may treat patients with severe uveitis even if a systemic disease is present, according to a study in the British journal of Ophthalmology. The retrospective study included 60 patients with uveitis; 41 patients had both uveitis and systemic disease. Patients underwent treatment with adalimumab with a mean follow-up of 87.9 weeks.

Effective outcome measures included visual acuity, anterior chamber cells, reduction of frequency of flares, decrease of macular edema and decrease of prednisone dose. Treatment was defined as effective when at least one factor improved and none worsened.

Forty-nine patients had at least one criterion improve and none worsen. Eleven patients did not meet improvement standards and were given supplemental or alternative treatment.

Forty-seven patients were still on adalimumab at the final follow-up visit. Adalimumab was discontinued in 13 patients. Of these, eight discontinued treatment due to ineffectiveness, three discontinued due to side effects, one discontinued due to pregnancy and one died from a heart attack unrelated to adalimumab. There were no noted severe side effects.

Useful Vision Restored In Retinitis Pigmentosa Patients Who Received Subretinal Implant

More than half of patients with severe retinitis pigmentosa who received the Alpha IMS subretinal implant recovered functional vision, according to results from a second human clinical trial of the device.

The trial examined nine patients for a 3- to 9-month period after subretinal implantation of the Alpha IMS a 3 mm × 3 mm, 1,500-pixel device designed to restore vision without externally visible equipment.

Each pixel has a photodiode, an amplification circuit and an electrode to allow an electrical impulse to be delivered to retinal layers corresponding to incoming light.

The chip, placed beneath the foveal region, works via inductive energy transfer from a battery pack in the control unit that allows the user to adjust brightness and contrast of perception. It offers a 10° × 10° diamond-shaped visual field that is roughly 15° diagonal.

One subject was excluded from follow-up due to intraoperative complications, but five of the remaining eight subjects reported functional vision improvements, including near vision recognition of facial characteristics and clothing patterns and ability to distinguish objects such as telephones, cutlery, door knobs and signs on doors. Far-vision improvements included ability to see the horizon and objects on the horizon.

A multicenter phase of the trial already has begun.

Another retinal implant for patients with advanced retinitis pigmentosa, the Argus II Retinal Prosthesis System (Second Sight Medical Products), was recently approved by the U.S. Food and Drug Administration.

Antibiotic Prophylaxis May Have Negative Effect On Safety Of Intravitreal Injections

A low rate of endophthalmitis after anti-VEGF intravitreal injections can be achieved without the use of preoperative and postoperative antibiotics. Antibiotic prophylaxis might, in fact, have a negative impact on the safety of the procedure, according to a speaker at the annual joint meeting of Ocular Surgery News and the Italian Society of Ophthalmology.

A study at the Bascom Palmer Eye Institute demonstrated that topical antibiotics before the day of injection did not reduce conjunctival bacterial counts more than the immediate pre-injection use of povidone-iodine. A Canadian study based on almost 16,000 injections suggested that the overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics compared with no antibiotics.

"In spite of this, the 2011 Patterns and Trends Survey of the American Society of Retina Specialists showed that 27% of retina specialists continue to use pre-injection antibiotics and 63% use post-injection antibiotics," according to the speaker.

Respiratory tract organisms of the streptococci species were found to be the most common cause of endophthalmitis with these procedures.