The human choroid is a heterogeneous, highly vascular connective tissue that dysfunctions in age-related macular degeneration (AMD). In this study, we performed single-cell RNA sequencing on twenty-one human choroids, eleven of which were derived from donors with early atrophic or neovascular AMD. Using this large donor cohort, we identified new gene expression signatures and immunohistochemically characterized discrete populations of resident macrophages, monocytes/inflammatory macrophages, and dendritic cells. These three immune populations demonstrated unique expression patterns for AMD genetic risk factors, with dendritic cells possessing the highest expression of the neovascular AMD-associated MMP9 gene. Additionally, we performed trajectory analysis to model transcriptomic changes across the choroidal vasculature, and we identified expression signatures for endothelial cells from choroidal arterioles and venules. Finally, we performed differential expression analysis between control, early atrophic AMD, and neovascular AMD samples, and we observed that early atrophic AMD samples had high expression of SPARCL1, a gene that has been shown to increase in response to endothelial damage. Likewise, neovascular endothelial cells harbored gene expression changes consistent with endothelial cell damage and demonstrated increased expression of the sialomucins CD34 and ENCM, which were also observed at the protein level within neovascular membranes. Overall, this study characterizes the molecular features of new populations of choroidal endothelial cells and mononuclear phagocytes in a large cohort of AMD and control human donors.

IMPORTANCE For research involving big data, researchers must accurately identify patients with ocular diseases or phenotypes of interest. Reliance on administrative billing codes alone for this purpose is limiting. OBJECTIVE To develop a method to accurately identify the presence or absence of ocular conditions of interest using electronic health record (EHR) data. DESIGN, SETTING, AND PARTICIPANTS This study is a retrospective analysis of the EHR data of patients (n = 122 339) in the Sight Outcomes Research Collaborative Ophthalmology Data Repository who received eye care at participating academic medical centers between August 1, 2012, and August 31, 2017. An algorithm that searches structured and unstructured (free-text) EHR data for conditions of interest was developed and then tested to determine how well it could detect the presence or absence of exfoliation syndrome (XFS). The algorithm was trained to search for evidence of XFS among a sample of patients with and without XFS (n = 200) by reviewing International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-9 or ICD-10) billing codes, the patient's problem list, and text within the ocular examination section and unstructured (free-text) data in the EHR. The likelihood that each patient had XFS was estimated using logistic least absolute shrinkage and selection operator (LASSO) regression. The EHR data of all patients were run through the algorithm to generate an XFS probability score for each patient. The algorithm was validated with review of EHRs by glaucoma specialists. MAIN OUTCOMES AND MEASURES Positive predictive value (PPV) and negative predictive value (NPV) of the algorithm were computed as the proportion of patients correctly classified with XFS or without XFS. RESULTS This study included 122 339 patients, with a mean (SD) age of 52.4 (25.1) years. Of these patients, 69 002 (56.4%) were female and 99 579 (81.4%) were white. The algorithm assigned a less than 10% probability of XFS for 121 085 patients (99.0%) as well as an XFS probability score of more than 75% for 543 patients (0.4%), more than 90% for 353 patients (0.3%), and more than 99% for 83 patients (0.07%). Validated by glaucoma specialists, the algorithm had a PPV of 95.0% (95% CI, 89.5%-97.7%) and an NPV of 100% (95% CI, 91.2%-100%). When there was ICD-9 or ICD-10 billing code documentation of XFS, in 86% or 96% of the records, respectively, evidence of XFS was also recorded elsewhere in the EHR. Conversely, when there was clinical examination or free-text evidence of XFS, it was documented with ICD-9 codes only approximately 40% of the time and even less often with ICD-10 codes. CONCLUSIONS AND RELEVANCE The algorithm developed, tested, and validated in this study appears to be better at identifying the presence or absence of XFS in EHR data than the conventional approach of assessing only billing codes; such an algorithm may enhance the ability of investigators to use EHR data to stud...

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No statistically significant difference was found in screening children from 1 to 3 years old compared with screening children >3 years old. These results confirm that early screening, before amblyopia is more pronounced, can reliably detect amblyogenic risk factors in children younger than 3 years of age, and we recommend initiation of photoscreening in children aged 1 year and older.

Precis: Gonioscopy-assisted transluminal trabeculotomy (GATT) is a novel technique that lowers intraocular pressure (IOP) by fracturing the trabecular meshwork. In this retrospective chart review, GATT was found to be effective at lowering the intraocular pressure for steroid-induced glaucoma (SIG). Purpose: GATT is a novel microinvasive glaucoma surgery that builds on traditional trabeculotomy techniques to decrease the proximal resistance of conventional outflow, and it is proposed to be an effective surgical treatment for SIG. The purpose of this study is to evaluate the efficacy of GATT for lowering the IOP in SIG. Methods and Patients: A retrospective chart review was performed of all GATT procedures performed on patients with a predominant diagnosis of steroid-induced glaucoma between March 1, 2016 and March 30,2018 at the University of Michigan. Primary outcome measures include IOP, the number of IOP-lowering medications prescribed, and the topical steroid dosing over the duration of follow-up. Results: A total of 13 patients with steroid-induced glaucoma underwent the GATT procedure. There was a significant reduction in the mean IOP at all postoperative visits. The average IOP decreased by 16.4 (55%) to 19.5 mm Hg (63%) between 3 and 24 months postoperatively. By 24 months, all patients had a reduction in IOP of >20%. The number of glaucoma medications also decreased significantly from an average of 3.1 medications preoperatively to an average of 0.8 medications at last follow-up. The majority of patients (>67%) required continued use of steroids at all postoperative visits. The most common postoperative complication was a transient hyphema (38%). No patients required a repeat glaucoma surgery or anterior chamber washout. Conclusions: This small case series suggests that GATT is an effective and safe surgical technique to decrease IOP and decrease medication burden in patients with predominantly steroid-induced glaucoma. To our knowledge, this is the first study looking specifically at the efficacy of GATT for predominantly SIG.

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Objective To assess long-term effects of genotype on chorioretinopathy severity in subjects with mitochondrial trifunctional protein (MTP) disorders. Design Retrospective case series. Participants Consecutive patients with MTP disorders evaluated at a single center from 1994 to 2015, including 18 subjects with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 subjects with trifunctional protein deficiency (TFPD). Methods Local records from all visits were reviewed. Every subject underwent complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine subjects underwent ancillary fundoscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures The primary outcome measure was best-corrected visual acuity (logMAR) at the final visit. Secondary outcome measures included spherical equivalent refraction, electroretinogram (ERG) b-wave amplitudes, and qualitative imaging findings. Results Subjects were followed for a median of 5.6 years (range 0.3–20.2). The median age of LCHADD subjects at initial and final visits was 2.3 and 11.9 years, while the median age for TFPD subjects at initial and final visits was 4.7 and 15.5 years. Four long-term survivors over the age of 16 years were included (three subjects with LCHADD and one subject with TFPD). LCHADD subjects demonstrated a steady decline in visual acuity from an average logMAR of 0.23 (Snellen equivalent 20/34) at baseline to 0.42 (Snellen equivalent 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow up. Subjects with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. ERG findings support the more severe clinical profile of LCHADD subjects compared with TFPD; the function of both rods and cones are diffusely attenuated in LCHADD but within normal limits for TFPD subjects. Conclusions Despite improved survival with early diagnosis, medical management, and dietary treatment, subjects with the LCHADD subtype of MTP disorder continue to develop visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

There is good potential for visual recovery following uncomplicated traumatic hyphema in children. In our patient cohort, the majority of patients had significant improvement in visual acuity within the first 28 days; in some children visual acuity continued to improve beyond the first month.