SENSITIVITY AND SPECIFICITY OF DETECTING POLYPOIDAL CHOROIDAL VASCULOPATHY WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis with structural en face optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Retrospective review of the medical records of eyes diagnosed with PCV by indocyanine green angiography with review of diagnostic testing with structural en face OCT and OCTA by a trained reader. Structural en face OCT, cross-sectional OCT angiograms alone, and OCTA in its entirety were reviewed blinded to the findings of indocyanine green angiography and each other to determine if they could demonstrate the PCV complex. Sensitivity and specificity of PCV diagnosis was determined for each imaging technique using indocyanine green angiography as the ground truth. RESULTS: Sensitivity and specificity of structural en face OCT were 30.0% and 85.7%, of OCT angiograms alone were 26.8% and 96.8%, and of the entire OCTA were 43.9% and 87.1%, respectively. Sensitivity and specificity were improved for OCT angiograms and OCTA when looking at images taken within 1 month of PCV diagnosis. CONCLUSION: Sensitivity of detecting PCV was low using structural en face OCT and OCTA but specificity was high. Indocyanine green angiography remains the gold standard for PCV detection.

Spectral-Domain Optical Coherence Tomography Angiography for the Diagnosis and Evaluation of Polypoidal Choroidal Vasculopathy.

PURPOSE: To compare the diagnostic ability of optical coherence tomography angiography (OCTA) with indocyanine green angiography (ICGA) in polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective review of 47 eyes with PCV imaged with ICGA and OCTA. For each eye, it was determined which imaging modality better delineated the PCV complex. The presence of a branching vascular network (BVN) and polyp(s) were noted. RESULTS: PCV was better visualized with ICGA in 21 eyes (44.7%) and with OCTA in 9 eyes (19.2%). The results were comparable in 17 eyes (36.2%). Of the 44 eyes with BVN on ICGA, 41 eyes (93.2%) also showed BVN on OCTA. Of the 28 eyes with polyp(s) on ICGA, 22 eyes (78.6%) also showed polyp(s) on OCTA. Polyps were high-flow lesions or faint low-flow dilations on OCTA. CONCLUSION: OCTA readily detects BVNs and can detect most polyps, but in many cases ICGA is better able to detect the PCV complex.

Prospective clinical trial of Intravitreal aflibercept treatment for PolypoIdal choroidal vasculopathy with hemorrhage or exudation (EPIC study): 6 month results.

BACKGROUND: Polypoidal choroidal vasculopathy is a variant of choroidal neovascularization and neovascular age related macular degeneration presenting with hemorrhagic and exudative changes within the macula and/or peripapillary region leading to vision loss. In contrast to neovascular age related macular degeneration, polypoidal choroidal vasculopathy has differing clinical manifestations and treatment strategies. Historically, polypoidal choroidal vasculopathy complexes are less responsive to anti-vascular endothelial growth factor therapy with no prospective clinical trials evaluating aflibercept in management of polypoidal choroidal vasculopathy. Herein we prospectively evaluate the efficacy and safety of intravitreal aflibercept in polypoidal choroidal vasculopathy. METHODS: A prospective, open-label, investigator-sponsored trial of intravitreal aflibercept for polypoidal choroidal vasculopathy in 21 eyes was conducted. Injections were administered monthly for 3 initial treatments, then every other month with monthly evaluations. The primary outcome measures were the mean change in best corrected visual acuity and adverse events. Secondary outcome measures included stabilization of vision, presence of subretinal hemorrhage, serous detachment, retinal pigment epithelial detachment, and regression of polypoidal complexes on indocyanine green angiography. RESULTS: At 6 months, the median visual acuity was 20/40 (range 20/25-20/200) with a mean Early Treatment Diabetic Retinopathy Study vision of 68.4 letters. There was a gain of 2.76 Early Treatment Diabetic Retinopathy Study letters at 6 months (p = 0.15). No patient developed severe vision loss (≤15 letters) and vision was stable or improved in 19/21 eyes (91 %). Subretinal fluid resolved in 13/18 eyes (72 %), and subretinal hemorrhage resolved in 6/8 eyes (75 %) respectively. The polyps regressed in 14/21 eyes (67 %) and the branching vascular network decreased in 1 eye and was stable in all other eyes. The retinal pigment epithelial detachment improved in 13/15 eyes (87 %). Bimonthly treatment occurred in 15/21 patients (71 %). There were no adverse events. CONCLUSIONS: Intravitreal aflibercept results in stabilization of vision, resolution of exudative and hemorrhagic complications with regression of polyps in polypoidal choroidal vasculopathy. Eyes with polypoidal choroidal vasculopathy previously treated with ranibizumab and bevacizumab can show marked improvement in the retinal pigment epithelial detachments and persistent polyps with aflibercept therapy. TRIAL REGISTRATION: Clinical trials.gov NCT01871376 , June 4(th) 2013.

Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study.

BACKGROUND AND OBJECTIVE: To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion. PATIENTS AND METHODS: Randomized, multicenter, comparative trial (ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1:1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline. RESULTS: The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], -288.3 to -137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, -309.6 to -178.0; P=.72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, -0.47 to -0.18; ranibizumab: 0.34 logMAR gain, 95% CI, -0.45 to -0.23; P=.38, ANOVA). CONCLUSION: In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity.

Polypoidal choroidal vasculopathy exudation and hemorrhage: results of monthly ranibizumab therapy at one year.

PURPOSE: To evaluate the efficacy and safety of monthly intravitreal injections of ranibizumab in patients with polypoidal choroidal vasculopathy (PCV) and active exudation or hemorrhage. METHODS: A prospective, single practice, open label trial of monthly intravitreal ranibizumab (0.5 mg) injections for PCV in 13 eyes of 13 patients who completed the 1-year study. The primary outcome measure was stabilization of vision (loss of <15 ETDRS letters). Secondary outcome measures included incidence of ocular and systemic adverse events, changes in subretinal hemorrhage, central foveal thickness, and polypoidal complexes on indocyanine green angiography at 1 year. RESULTS: No patient lost ≥ 15 letters in visual acuity at 1 year. Three patients (23%) gained ≥ 15 letters at 12 months. Subretinal hemorrhage resolved in 9/9 eyes (100%). Macular edema improved in 5/5 eyes (100%). Subretinal fluid completely resolved in 4/9 eyes (44%), decreased in 2/9 eyes (22%), and increased in 3/9 eyes (33%). Polypoidal complexes decreased in 5/13 eyes (38%). CONCLUSION: Continuous monthly intravitreal ranibizumab decreases leakage and hemorrhage in eyes with exudative and hemorrhagic complications of PCV. Branching vascular networks persisted, and polypoidal complexes decreased in only 5/13 (38%) eyes with continuous antiangiogenic therapy at 1 year.

Genetics of birdshot chorioretinopathy.

Birdshot chorioretinopathy is a bilateral, posterior uveitis that affects primarily Caucasians. Although the genetic basis of disease is not completely understood, certain factors are known, such as the strong association with human leukocyte antigen (HLA)-A29. However, given the prevalence of the HLA-A29 allele in the general population, if it were the only factor required for disease, many more people would have birdshot chorioretinopathy. It has been suggested that some environmental factor may trigger this disease entity in those who are genetically predisposed based on inheritance of the HLA-A29 allele.

Sleep disturbances in young subjects with visual dysfunction.

PURPOSE: To determine whether the type of ophthalmic disease is predictive of sleep and wakefulness disturbances in young subjects with visual dysfunction. DESIGN: Prospective cohort study. PARTICIPANTS AND CONTROLS: Twenty-five subjects (ages 12-20) were recruited from the Missouri School for the Blind. Twelve controls with normal sight were recruited from a residential school. METHODS: Daily activity was monitored for 14 days using wrist actigraphy. Sleep and wakefulness measures were derived from actigraphy records by automated analysis. Visually impaired subjects were prospectively stratified by presence or absence of optic nerve disease. MAIN OUTCOME MEASURES: Daytime napping and regularity of awakening time (wake-up time instability). RESULTS: Subjects with optic nerve disease napped in the daytime significantly more than other visually impaired children or normal sighted controls: 28.1+/-4.0 minutes per day (mean +/- standard error) versus 11.9+/-2.4 minutes per day in equally visually impaired subjects with intact optic nerve function versus 6.2+/-2.2 minutes per day in subjects with normal sight (P<0.0001). These subjects also showed significantly more variable awakening times than the other groups. Logistic regression revealed that subjects with optic nerve disease are 9.1 times more likely to demonstrate daily napping of more than 20 minutes per day than equally blind subjects without optic nerve disease (95% confidence interval [CI] = 1.4-58.7, P = 0.02). Blind subjects with optic nerve disease are 21.3 times more likely than children with normal sight to nap more than 20 minutes on average per day (95% CI = 1.2-378, P = 0.04). CONCLUSIONS: Optic nerve disease is predictive of increased daytime napping in young visually impaired subjects, suggesting that the nature and presence of ophthalmic disease affect the probability of concomitant sleep timing disorders.

Loss of photic entrainment and altered free-running circadian rhythms in math5-/- mice.

Mammalian free-running circadian rhythms are entrained to the external light/dark cycle by photic signaling to the suprachiasmatic nuclei via the retinohypothalamic tract (RHT). We investigated the circadian entrainment and clock properties of math5-/- mutant mice. math5 is a critical regulator of retinal ganglion cell development; math5-/- mice show severe optic nerve hypoplasia. By anterograde cholera toxin B tracing, we find that math5-/- mice do not develop an identifiable RHT pathway. This appears to be attributable to agenesis or dysgenesis of the majority of RHT-projecting retinal ganglion cells. math5-/- mice display free-running circadian rhythms with a period approximately 1 hr longer than B6/129 controls (24.43 +/- 0.10 vs 23.62 +/- 0.19 hr; p < 0.00001). The free-running period of heterozygote mice is indistinguishable from that of controls. math5-/- mice show no entrainment to light/dark cycles, whereas heterozygote mice show normal entrainment to both 12 hr light/dark cycles and to a 1 hr skeletal photoperiod. math5-/- mice show reduced ability to entrain their rhythms to the nonphotic time cue of restricted running wheel access but demonstrate both free-running behavior and entrained anticipation of wheel unlocking in these conditions, suggesting the presence of a second diurnal oscillatory system in math5-/- animals. These results demonstrate that retinal ganglion cell input is not necessary for the development of a free-running circadian timekeeping system in the suprachiasmatic nucleus but is important for both photic entrainment and determination of the free-running period.