PURPOSE: To evaluate the defocus curves of 4 presbyopia-correcting intraocular lenses (IOLs). SETTING: Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN: Prospective case series. METHODS: Patients included in the study had bilateral surgery with implantation of diffractive panfocal, diffractive trifocal, segmental refractive (SegRef), or extended-depth-of-focus (EDOF) presbyopia-correcting IOLs. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, uncorrected intermediate and near visual acuities, distance-corrected intermediate (DCIVA) and near (DCNVA) visual acuities, defocus curve, and spectacle independence were measured. RESULTS: The UDVA and CDVA were not significantly different between groups (P > .05); however, the EDOF group had worse near CDVA (P < .001). The trifocal and EDOF groups showed better DCIVA than the panfocal and SegRef group at 80 cm (P < .001); the EDOF and panfocal groups had comparable DCIVA at 60 cm (P > .05). Defocus curves showed no significant between-group differences from 4 m to 2 m (P > .05). The EDOF group had better visual acuity from 1 m to 67 cm than the trifocal and SegRef groups and better visual acuity than the panfocal group at 1 m (P > .05). Compared with the other IOLs, the panfocal IOL yielded significantly better visual acuity at 50 cm (P < .001) and the EDOF IOL worse visual acuity at 40 cm (P < .01). There was a significant difference in spectacle independence between the panfocal group and EDOF group (P < .05) but no difference between the other groups. CONCLUSIONS: The 4 IOLs provided equally good CDVA. The EDOF IOL yielded slightly better DCIVA but worse DCNVA than the other IOLs. Only the panfocal IOL gave better DCIVA at 50 cm.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1 mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.

The gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work.

Purpose: To determine the importance of various vision parameters to functionality in glaucoma. Methods: Vision was measured using seven parameters: visual acuity (VA), contrast sensitivity (CS), integrated visual field (IVF), area under the log CS function (AULCSF), color vision, stereoacuity, and VA with noise (ViN). Likelihood ratio testing (LRT) determined if the full set of visual parameters significantly explained variability in 10 functional outcomes. For outcomes where the visual contribution was significant, dominance analysis determined the relative importance of the various visual parameters. Results: The analysis included 151 glaucoma patients. Mean age was 70 ± 6.8 years, and 47% were men. Significant visual contributions (LRT P < 0.05) were noted for glaucoma quality of life (GQL-15), reading speed, driving cessation, daily steps, and base of support while walking, but not for fear of falling, balance, gait velocity, stride velocity, and stride length while walking (LRT P > 0.05). The most important parameter (and percent contribution) to vision-explained variability were AULCSF for daily steps (45%), IVF for base of support (35%), VA for reading speed (34%), CS for GQL-15 (30%), and VA for driving cessation (26%). Conclusions: Measures of visual ability are important for several aspects of quality of life and functionality. The most important vision parameter for functionality differs depending on the domain studied. Reading and driving were explained by VA and IVF sensitivity. On the other hand, GQL-15 and daily steps were more heavily influenced by CS and AULCSF, which are rarely performed clinically.

PURPOSE: To investigate the association between choroidal thickness and persistent subretinal fluid (PSF) after surgery for recent-onset rhegmatogenous retinal detachment (RRD). DESIGN: Case-control study. PARTICIPANTS: Fourteen eyes with macula-off RRD (with fovea on and off) that achieved retinal reattachment on funduscopy and demonstrated PSF after surgery (PSF group) were compared with 62 eyes with macula-off RRD (with fovea on and off) that did not demonstrate PSF after surgery (non-PSF group). METHODS: The diagnosis of PSF was made by the detection of subretinal fluid pockets on OCT beyond 6 weeks after surgery. Covariates included baseline demographics, duration of RRD, area of RRD, foveal status, method of subretinal fluid drainage, retinal pigment epithelium (RPE) changes, and choroidal thickness in both eyes. Multivariate regression analysis was performed by adding gender, age, and pathologic myopia into the model. The secondary outcomes included postoperative vision and time to resolution of PSF. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness in affected eyes, measured by enhanced depth imaging OCT images. RESULTS: The percentage of eyes that underwent vitrectomy, scleral buckle surgery, and pneumatic retinopexy were 71.4%, 14.3%, and 14.3% in the PSF group, respectively, and 87.1%, 11.3%, and 1.6% in the non-PSF group, respectively. Eyes with PSF showed significantly thicker subfoveal choroid than eyes without PSF (305±61 μm vs. 200±70 μm, respectively; adjusted difference, 78.6±19.1 μm; 95% confidence interval [CI], 40.3-116.8 μm; P < 0.001). The PSF group demonstrated a greater proportion of RPE changes in fellow eyes (30.8% vs. 1.7%; P = 0.03) and significantly worse best-corrected visual acuity at the 12-month follow-up (P = 0.03). Multiple logistic regression analysis revealed that choroidal thickness of 280 μm or more was a significant factor associated with the presence of PSF (adjusted odds ratio [AOR], 13.4; 95% CI, 3.1-34.7 [P = 0.001]. CONCLUSIONS: Persistent subretinal fluid is associated with increased subfoveal choroidal thickness in surgical and fellow eyes and with RPE changes in the fellow eye. This indicates that PSF likely belongs to the pachychoroid spectrum. In affected eyes, PSF tends to persist for more than 1 year and results in delayed visual recovery.

The purpose of this review was to identify areas of consensus and disagreement among experts for the definition of success following strabismus surgery using the Delphi process. Three rounds of electronic questionnaires were sent to a panel of 28 strabismus experts. Throughout the process, members of the panel were masked to one another's identities to minimize the possibility of influence among members. Prior to data collection, we defined consensus as an 85% agreement on the answer to each question. Questions for which there was no consensus were reworded, and the resultant new questions were used in each subsequent round of questioning. We arrived at consensus for 23 of the 36 questions (64%). Consensus was obtained for recommending unique criteria for the definition of success for certain specific strabismus conditions. In addition, it was considered important that stereopsis and the range of single binocular vision be included in the definition of success for certain types of strabismus.

PURPOSE: To review the roles of analytic and innovative thought in advancing knowledge, using past examples in ophthalmology, and to explore potential strategies to improve our understanding of age-related macular degeneration (AMD) and develop new therapies. DESIGN: Presented as the 2018 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on October 26, 2018. PARTICIPANTS: None. METHODS: Review of published literature and sources on creativity and innovation. MAIN OUTCOME MEASURES: Recommendations for future AMD research. RESULTS: Innovative solutions to problems often seem intuitively obvious in hindsight. Yet, some problems seem impossible to solve. In the 1990s, AMD was a significant unmet need, with only destructive therapies for neovascular disease. This changed with the development of 2 therapies: (1) verteporfin photodynamic therapy (PDT) and (2) anti-vascular endothelial growth factor (VEGF) therapies, which are now administered to millions of people annually around the world. Now, we are frustrated by the lack of therapies for early and intermediate AMD and geographic atrophy. Photodynamic therapy and anti-VEGF drug development occurred through a combination of analytic thought and creative disruption through innovation. To get past our current impasse in understanding and treating AMD, we need to harness both analysis and innovation. We have many important building blocks in place-information on genetics, clinical findings, imaging, and histology-and have identified key pathways and potential therapeutic targets. Perhaps we need additional investigation, analysis, and integration to improve our understanding through work on structure/function and genotype/phenotype correlations and development of imaging and systemic biomarkers. We likely also need an innovative disruption. This innovation might be the concept that there are subtypes of early and intermediate AMD characterized by specific clinical phenotypes, genotype, functional characteristics, and biomarkers that are dependent on particular pathways and treatable with a specific agent. We need to encourage innovation in each of us within our research and clinical community. CONCLUSIONS: Although we have accumulated extensive knowledge about AMD, we are currently at an impasse in the development of new treatments. We need to continue the analytic process, but at the same time encourage innovative disruption to develop successful AMD therapies.