End-of-Study Results for the Ladder Phase 2 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, randomized, active treatment-controlled phase 2 clinical trial. PARTICIPANTS: Patients diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (N = 220). METHODS: Patients were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections. MAIN OUTCOME MEASURES: End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. RESULTS: At study end, the mean time on study was 22.1 months (range, 10.8-37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients went 12 months or longer without meeting refill criteria in the PDS 10-mg/ml, 40-mg/ml, and 100-mg/ml treatment arms, respectively. At month 22, the observed mean BCVA change from baseline was ‒4.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒2.3 ETDRS letters, +2.9 ETDRS letters, and +2.7 ETDRS letters in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg treatment arms, respectively. At month 22, the observed mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg treatment arms. No new safety signals were detected during the additional follow-up. CONCLUSIONS: Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.

Mitochondrial variant G4132A is associated with familial non-arteritic anterior ischemic optic neuropathy in one large pedigree.

OBJECTIVE: To identify the genetic factors associated with familial non-arteritic anterior ischemic optic neuropathy (NA-AION) in a large pedigree. METHODS: Eleven family members of a single pedigree, including six affected with NA-AION, underwent detailed clinical examinations. The mitochondrial DNA of the proband was sequenced in its entirety in search of disease-causing mutations associated with NA-AION in the pedigree. A control panel comprising 1488 patients suspected of having Leber hereditary optic neuropathy (LHON) and 97 general-population control subjects was screened for the mitochondrial sequence variant identified in the family. RESULTS: Affected family members were all male and exhibited classic features of NA-AION. Their mean age was 50.2 +/- 5.0 years. A total of 23 sequence variations were detected in the mitochondrial genome of the proband, including one novel sequence variation (G4132A, Ala276Thr) in the NADH dehydrogenase subunit 1 gene (ND1). The G4132A mitochondrial variant was detected in six members of a single pedigree with NA-AION. The G4132A variation was not observed in any of the 1585 subjects in the control panel. Moreover, this variant was not identified in over 2469 ethnically diverse individuals previously evaluated through the Human Mitochondrial Genome Database. None of the three major mutations associated with LHON (G3460A, G11778A, T14484C) were identified in the family. CONCLUSION: The G4132A mitochondrial variation is associated with familial NA-AION in our pedigree.

Bimanual phacoemulsification through 2 stab incisions. A wound-temperature study.

PURPOSE: To determine the thermal parameters of bimanual ultrasound-based phacoemulsification through 2 stab incisions with a bare aspiration needle. SETTING: In vitro laboratory. METHODS: The Sovereign phacoemulsification unit (Allergan) was used in 3 modes in conjunction with the Olson irrigating chopper (ASICO) in 6 fresh human cadaver eye-bank eyes to determine the temperature at which a wound burn would occur. A wound burn was defined as temperature exceeding 45 degrees C, whitening around the wound, or wound contraction. RESULTS: One hundred percent ultrasound power was required to create a wound burn in the unoccluded mode in continuous ultrasound and the burst mode. The time to create the wound burn was 160 and 180 seconds in 2 eyes in continuous ultrasound and 42 and 50 seconds in 2 eyes in the burst mode; it was 58 and 70 seconds in continuous ultrasound with complete occlusion and required 80% power. CONCLUSIONS: The energy necessary to obtain a wound burn during 2-incision bimanual ultrasound-based phacoemulsification with a bare aspiration needle in human cadaver eyes was extremely high. The parameters necessary to create a wound burn in each modality occurred well beyond normal clinical settings and provide evidence that 2-stab ultrasound-based lens extraction can be performed safely with the Sovereign machine.

Microphacoemulsification with WhiteStar. A wound-temperature study.

PURPOSE: To verify the temperature-induction effect of bimanual ultrasound-based phacoemulsification through 2 stab incisions with a bare aspiration needle and new proprietary technology. SETTING: In vitro laboratory. METHODS: The Sovereign phacoemulsification unit and the WhiteStar system (Allergan) were used in conjunction with the Olson irrigating chopper (ASICO) and a 19-gauge bare phaco needle in 2 human cadaver eye-bank eyes at 100% power unoccluded, 100% power with aspiration completely occluded, and 100% power with aspiration and flow completely occluded. Temperature data were monitored throughout the experiment. Any sign of a wound burn, defined as temperature exceeding 45 degrees C, whitening around the wound, or wound contraction, was the end point. RESULTS: At 100% continuous phacoemulsification power, the temperature did not rise above 27.3 degrees C. When the aspiration line was totally occluded at 100% continuous power, the temperature did not rise above 32.5 degrees C. When flow into the eye and aspiration were completely occluded at 100% power, a wound change and temperature of 45 degrees C occurred in 45 seconds in the first eye and in 29 seconds in the second eye. CONCLUSIONS: Using the Sovereign phacoemulsification unit with the WhiteStar system during 2-stab-incision bimanual microphacoemulsification with a bare 19-gauge aspiration needle in human cadaver eyes, a wound burn could not be produced at the highest energy settings unless all flow into the eye and all aspiration were occluded. These settings were well beyond clinically applicable conditions and provide evidence that microphacoemulsification can be performed safely with the WhiteStar system.

Optic neuropathy due to anaplastic large cell lymphoma.

PURPOSE: To report a case of anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) producing an optic neuropathy. METHODS: Observational case report. RESULTS: A 29-year-old male presented with new onset headaches. Magnetic resonance imaging (MRI) of the brain revealed a large enhancing parietal lobe mass. Ocular exam at that time was normal. Initial diagnoses included possible bacterial cerebritis and fungal abscess. Serial lumbar punctures showed increased white blood cells but cytology was negative. A brain biopsy was non-diagnostic. The patient then presented with a left optic neuropathy. Repeat MRI of the brain and orbits revealed infiltration of the clivus and left orbital apex including the optic nerve. The patient had elevated liver function studies and an abdominal ultrasound disclosed two hypoechoic lesions. Liver biopsy confirmed the diagnosis of ALK-1 positive ALCL. The patient was treated with chemotherapy but expired seven months after the initial presentation. CONCLUSION: ALCL should be considered to be a very rare but potential cause of optic neuropathy. To our knowledge, this is the first reported case of ALCL causing an optic neuropathy.