Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Purpose To qualitatively and quantitatively compare Optos© fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon© fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in uveitis patients. Design Retrospective, observational case series. Methods Images of all uveitis patients imaged with same-sitting Optos FA and 9-field montage FA during a 9 month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage. Results The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm2 vs. 4.8 mm2, P<0.0001). Twenty-two of 49 (45%) eyes with gradable photos had at least 25% more leakage on the Optos image than on the montage image. Two (4.1%) had at least 25% less leakage on Optos, and 25 (51%) were similar between the two modalities. Two eyes had no apparent retinal vascular leakage on 9-field montage but were found to have apparent leakage on Optos images. Twenty-three of the 49 eyes had posterior pole leakage, and of these 17 (73.9%) showed more posterior pole leakage on the Optos image. A single 200 degree Optos FA image captured a mean 1.50x the area captured by montage photography. Conclusion More retinal vascular pathology, both in the periphery and the posterior pole, is seen with Optos FA in uveitis patients when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.

Background Recent evidence suggests that neovascular age-related macular degeneration (AMD) may have an immune mediated component. Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. This small short-term pilot study assesses the safety of subconjunctival Palomid 529 in the treatment of neovascular AMD, with some limited efficacy information. Methods In this 12-week phase I open-label prospective pilot study, five participants with neovascular age-related macular degeneration that were refractory to intravitreal anti-vascular endothelial growth factor (VEGF) received three serial monthly subconjunctival doses of 1.9 mg Palomid 529. All participants were also offered concomitant monthly intravitreal anti-VEGF injections. Safety was monitored via adverse events recording. Additional outcome measures included visual acuity, optical coherence tomography, fluorescein angiography, indocyanine green angiography and fundus photography. Results The study drug was well-tolerated by all participants. There were no drug-related adverse events and no serious adverse events. A depot formed at the injection site, which persisted at the end of the study. In these anti-VEGF refractory patients, no clinically important changes in best-corrected visual acuity, fluorescein leakage pattern, choroidal neovascularization size on indocyanine green angiography, or autofluorescence pattern on fundus autofluorescence were observed compared to baseline. The fluid status, assessed with optical coherence tomography showed that central retinal thickness and macular volume remained stable in three participants, while the other two participants clinically progressed. Conclusions Serial subconjunctival injections of Palomid 529 were well-tolerated and resulted in depot formation. There were no concerns for any ocular or systemic toxicity during this small short-term study. Larger randomized studies are required to determine efficacy.

Purpose To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Design Post-hoc analysis of a prospective clinical study. Participants 69 participants with nAMD in at least one eye. Methods Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Main Outcome Measures Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Results Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). Conclusions While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti-VEGF treatment.

Purpose To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. Design Observational case review. Participants Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. Methods Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. Main Outcome Measures Visual acuity, size of RCH, and degree of exudation. Results Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. Conclusions Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other medications in the same class or drugs directed at multiple targets in the tumor, may be safer and more effective for the treatment of advanced VHL-associated RCH.

The authors report a case of trigeminal neuralgia developed after vitreoretinal surgery. Clinicians should consider trigeminal neuralgia in the differential diagnosis of atypical pain after retinal surgery.

Purpose The purpose of this one-year prospective study was to investigate how induction/pro re nata (PRN) ranibizumab intravitreal treatment of eyes with neovascular age related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. Methods High speed indocyanine green angiography (HS-ICG) measurements provided quantification of the CNV size in 60 patients followed for one year. Minimum intensity projection optical coherence tomography (minIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography (FA) was also assessed to evaluate late retinal leakage. Results After one year, mean area of CNV measured with ICG decreased by 5.8%. MinIP OCT mean area of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of FA leakage decreased by 6.3%. Both the area of outer retinal disruption measured with minIP OCT and the area of leakage on FA typically exceeded the area of CNV on ICG at baseline and one year. Conclusion CNV treated with induction/PRN intravitreal ranibizumab for one year essentially remained static. MinIP OCT suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on ICG and minIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.