Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.

PURPOSE: To evaluate the finding of anomalous superior oblique muscles in congenital fibrosis of the extraocular muscles (CFEOM), a feature not previously emphasized in this condition. METHODS: The medical records of all patients clinically or genetically diagnosed with CFEOM at Boston Children's Hospital between 2010 and 2018 were reviewed retrospectively. Those who underwent strabismus surgery during the study period were included in the analysis. Baseline patient characteristics, type of CFEOM, results of genetic testing, and intraoperative features of the superior oblique muscle or tendon were recorded. RESULTS: Of 24 patients identified (age range, 1 month to 62 years), 10 (42%) had genetically confirmed CFEOM, and 22 underwent strabismus surgery, 14 (64%) involving the superior oblique muscle. Of these, 7 (50%) had anomalously inserted tendons (most commonly attached nasal to the superior rectus muscle), whereas 7 (50%) had increased superior oblique muscle tension. CONCLUSIONS: Half of CFEOM patients who underwent superior oblique surgery had abnormally inserted superior oblique tendons, and 50% had tight muscles or abnormally thin tendons, findings that have not been well-characterized in this condition. The findings suggest that abnormal insertion of the superior oblique muscles and tendons are additional features of the disease process in CFEOM that have not been described previously. These features may contribute to the severe upgaze limitation in CFEOM and highlight the importance of superior oblique tenotomy in surgical management.

: To describe the rationale, design, methodology and baseline characteristics of Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), a community-based prospective cohort study in patients with type 2 diabetes mellitus (T2DM) living in northeast China.: Patients with T2DM, aged 30 years and above from communities of Fushun city, Liaoning province, China, were recruited. The presence and severity of the diabetic retinopathy (DR) were determined by a modified Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale of 6 fields fundus photographs. Detailed ocular examinations and questionnaires were collated, in addition to blood and urine sample collection.: Of the 2224 subjects eligible for the FS-DIRECT, 2033 (91.4%) participated in the study. The majority of participants were female (58.9%), the average age was 62.1 ± 9.1 years. The overall prevalence rates of DR, non-proliferative DR, proliferative DR, diabetic macular edema, and vision-threatening retinopathy were 44.3%, 40.0%, 4.3%, 15.2%, and 12.3%, respectively. Compared to the patients without DR, patients with DR had lower income, an earlier onset of diabetes, a longer duration of diabetes, higher proportion of insulin use, higher fasting plasma glucose, HbA1c, systolic blood pressure, total cholesterol and high density lipoprotein, as well as a higher level of urine protein (all < .05).: The baseline data of FS-DIRECT showed a high prevalence of DR in a community of northeast China. Further investigation will provide key information about the risk factors, impact, and trends of DR in this region.

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.

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.