Predictors of Long-term Ophthalmic Complications after Closed Globe Injuries Using the Intelligent Research in Sight (IRIS®) Registry.

Purpose: To identify clinical factors associated with the need for future surgical intervention following closed globe ocular trauma. Design: Retrospective cohort study. Subjects Participants and/or Controls: Patients in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry with a diagnosis of closed globe ocular trauma occurring between 2013 and 2019, identified using International Classification of Disease, 10th Revision and Systematized Nomenclature of Medicine codes. Methods: Diagnosis codes were used to identify multiple concomitant diagnoses present on the date of closed globe ocular trauma. Survival analyses were performed for each outcome of interest, and linear regression was used to identify clinical factors associated with the risk of surgical intervention. Main Outcome Measures: Outcomes included retinal break treatment, retinal detachment (RD) repair, retinal break treatment or RD repair, glaucoma surgery, and cataract surgery. Results: Of the 206 807 patients with closed globe ocular trauma, 9648 underwent surgical intervention during the follow-up period (mean, 444 days): 1697 (0.8%) had RD repair, 1658 (0.8%) had retinal break treatment, 600 (0.3%) had glaucoma surgery, and 5693 (2.8%) had cataract surgery. Traumatic cataract was the strongest risk factor for cataract surgery (hazard ratio, 13.0; 95% confidence interval, 10.8-15.6), traumatic hyphema showed highest risk for glaucoma surgery (7.24; 4.60-11.4), and vitreous hemorrhage was the strongest risk factor for retinal break treatment and detachment repair (11.01; 9.18-13.2 and 14.2; 11.5-17.6, respectively) during the first 60 days after trauma date. Vitreous hemorrhage was a risk factor for cataract surgery at > 60 days after trauma date only. Iris-angle injury was the strongest risk factor for glaucoma surgery > 60 days after trauma, while vitreous hemorrhage remained the strongest factor for retinal break treatment and detachment repair at > 60 days. Traumatic hyphema was a risk factor for all surgical outcomes during all follow-up intervals. Conclusions: Diagnosis of concomitant traumatic cataract, vitreous hemorrhage, traumatic hyphema, and other risk factors may increase the likelihood of requiring surgical intervention after closed globe ocular trauma.

Association of Environmental Factors with Age-Related Macular Degeneration using the Intelligent Research in Sight Registry.

Purpose: Investigate associations of natural environmental exposures with exudative and nonexudative age-related macular degeneration (AMD) across the United States. Design: Database study. Participants: Patients aged ≥ 55 years who were active in the IRIS Registry from 2016 to 2018 were analyzed. Patients were categorized as nonexudative, inactive exudative, and active exudative AMD by International Classification of Diseases 10th Revision and Current Procedural Terminology (CPT) codes. Patients without provider-level ZIP codes matching any ZIP code tabulation area were excluded. Methods: Environmental data were obtained from public sources including the US Geological Survey, National Renewable Energy Laboratory, National Oceanic and Atmospheric Administration, and Environmental Protection Agency. Multiple variable, mixed effects logistic regression models with random intercepts per ZIP code tabulation area quantified the association of each environmental variable with any AMD versus non-AMD patients, any exudative AMD versus nonexudative AMD, and active exudative AMD versus inactive exudative and nonexudative AMD using 3 separate models, while adjusting for age, sex, race, insurance type, smoking history, and phakic status. Main Outcome Measure: Odds ratios for environmental factors. Results: A total of 9 884 527 patients were included. Elevation, latitude, solar irradiance measured in global horizontal irradiance (GHI) and direct normal irradiance (DNI), temperature and precipitation variables, and pollution variables were included in our models. Statistically significant associations with active exudative AMD were GHI (odds ratio [OR], 3.848; 95% confidence interval [CI] with Bonferroni correction, 1.316-11.250), DNI (OR, 0.581; 95% CI, 0.370-0.913), latitude (OR, 1.110; 95% CI, 1.046-1.178), ozone (OR, 1.014; 95% CI, 1.004-1.025), and nitrogen dioxide (OR, 1.005; 95% CI, 1.000-1.010). The only significant environmental associations with any AMD were inches of snow in the winter (OR, 1.005; 95% CI, 1.001-1.009) and ozone (OR, 1.011; 95% CI, 1.003-1.019). Conclusions: The strongest environmental associations differed between AMD subgroups. The solar variables GHI, DNI, and latitude were significantly associated with active exudative AMD. Two pollutant variables, ozone and nitrogen dioxide, also showed positive associations with AMD. Further studies are warranted to investigate the clinical relevance of these associations. Our curated environmental dataset has been made publicly available at https://github.com/uw-biomedical-ml/AMD_environmental_dataset.

Demographics and Seasonality of Retinal Detachment, Retinal Breaks, and Posterior Vitreous Detachment from the Intelligent Research in Sight Registry.

Purpose: To investigate the incidence, seasonal variation, and differences among age, sex, and race for rhegmatogenous retinal detachment (RRD) repair, retinal break (RB) treatment, and posterior vitreous detachment (PVD) in the Intelligent Research in Sight (IRIS) Registry. Design: Retrospective database study. Participants: Patients in the IRIS Registry who underwent RRD repair, RB treatment, or cataract surgery (CS) based on Current Procedural Terminology codes and PVD diagnosis based on International Classification of Diseases, Ninth and Tenth Revision, codes. Methods: Daily incidence rates were defined as the ratio of patients who underwent RRD repair or RB treatment and patients with a diagnosis of PVD to the total number of patients followed on a given day within the IRIS Registry. The CS group was included as a comparison for seasonal variation. Rates were stratified by decade of life, sex, and race. Main Outcome Measures: Time series trends for incidence rates of RRD, RB, and PVD. Results: A total of 7 115 774 patients received a diagnosis of incident PVD, 237 646 patients underwent RRD repair, and 359 022 patients underwent RB treatment. Also included were 5 940 448 patients who underwent CS. The mean daily incidence for RRD repair, RB treatment, PVD diagnosis, and CS were 0.46 per 100 000 patients, 0.70 per 100 000 patients, 13.90 per 100 000 patients, and 11.80 per 100 000 patients, respectively. Men showed higher incidence of RRD repair and RB treatment than women, whereas women showed higher incidence of PVD diagnosis. Rhegmatogenous retinal detachment incidence was higher in White people compared with other races. Seasonal decreases in PVD, RB treatment, RRD repair, and CS corresponded to national holidays, with larger decreases in winter months. Kaplan-Meier estimates showed that RRD repair and RB treatment typically occurred within 60 days of PVD diagnosis. Conclusions: Within the IRIS Registry, the highest incidence of RRD was in the 6th and 7th decade of life. There was a higher incidence of RRD repair and RB treatment in men compared with women. The seasonal variation associated with national holidays was less pronounced for RRD repair and RB treatment.

Grading Anterior Chamber Inflammation with Anterior Segment Optical Coherence Tomography: An Overview.

The objective grading of anterior chamber inflammation (ACI) has remained a challenge in the field of uveitis. While the grading criteria produced by the Standardization of Uveitis Nomenclature (SUN) International Workshop have been widely adopted, limitations exist including interobserver variability and grading confined to discrete categories rather than a continuous measurement. Since the earliest iterations of optical coherence tomography (OCT), ACI has been assessed using anterior segment OCT and shown to correlate with slit-lamp findings. However, widespread use of this approach has not been adopted. Barriers to standardization include variability in OCT devices across clinical settings, lack of standardization of image acquisition protocols, varying quantification methods, and the difficulty of distinguishing inflammatory cells from other cell types. Modern OCT devices and techniques in artificial intelligence show promise in expanding the clinical applicability of anterior segment OCT for the grading of ACI.

IDIOPATHIC PENETRATION OF CILIA INTO THE POSTERIOR SEGMENT PRESENTING AS SECTORAL SCLERITIS WITH PROGRESSIVE INTRAOCULAR INFLAMMATION.

PURPOSE: To report two cases of idiopathic intraocular cilia presenting as sectoral scleritis with progressive intraocular inflammation. METHODS: Both patients were treated with intravitreal antibiotics and underwent pars plana vitrectomy where the cilia were removed and identified on histopathology. RESULTS: One patient developed a retinal detachment while being treated for presumed endophthalmitis. The intraocular cilium was discovered during pars plana vitrectomy. In the second case, the cilium was detected on dilated fundus exam and was believed to be the cause of the patient's scleritis and vitritis. Therapeutic vitrectomy was performed. In both cases, the cilia were positively identified on histopathology. CONCLUSION: Idiopathic intraocular penetration of cilia should be considered in the differential diagnosis of sectoral scleritis with progressive intraocular inflammation.

A Case of Bilateral Multifocal Choroiditis Associated with BRAF/MEK Inhibitor Use for Metastatic Cutaneous Melanoma.

PURPOSE: To report a case of BRAF/MEK inhibitor-associated multifocal choroiditis that recurred after medication re-exposure and resolved after discontinuing BRAF/MEK inhibition and administering local steroid therapy. CASE REPORT: A 32-year-old woman with metastatic cutaneous melanoma on dabrafenib/trametinib presented with bilateral anterior uveitis and new bilateral multifocal chorioretinal scars. The anterior uveitis resolved after a course of topical steroids. She presented 18 months later with reactivation of bilateral multifocal choroiditis after starting encorafenib/binimetinib 1 month prior. The chorioretinal lesions appeared elevated with associated vitreous cell. Indocyanine angiography showed numerous foci of new choroiditis, more pronounced in the left eye. Encorafenib/binimetinib was discontinued and a subtenon triamcinolone injection was administered to the left eye. Her symptoms improved and the choroiditis resolved. CONCLUSION: BRAF/MEK inhibitors may be associated with ocular toxicity manifesting as multifocal choroiditis. The increasing use of these agents and risk of visual impairment warrants early detection and management.

Bilateral Ampiginous Choroiditis following Presumed SARS-CoV-2 Infection.

PURPOSE: To report a case of bilateral ampiginous choroiditis following presumed SARS-CoV-2 infection. Case Description. A 25-year-old woman presented with metamorphopsia and a paracentral scotoma in her left eye. She endorsed night sweats, headache, and new-onset anosmia beginning 1 week before her visual symptoms. She also had multiple confirmed ill COVID-19 contacts at her workplace before the onset of her symptoms. Funduscopic examination and multimodal imaging revealed placoid lesions in the macula and midperiphery of both eyes consistent with ampiginous choroiditis. COVID-19 antibody testing returned positive for IgG, and an extensive systemic evaluation was otherwise unremarkable. She was treated with oral prednisone and azathioprine with stabilization of the retinal lesions and no progression of her symptoms. CONCLUSIONS: Ampiginous choroiditis is an inflammatory chorioretinopathy with an unknown pathogenic mechanism that often necessitates early immunomodulatory therapy. This report suggests that SARS-CoV-2 infection may trigger chorioretinal inflammation in susceptible hosts.

Hemorrhagic choroidal detachment as the presenting sign of uveal melanoma.

PURPOSE: To describe two cases of medium-sized uveal melanoma presenting with hemorrhagic choroidal detachments. OBSERVATIONS: The first case is a 39-year-old man who presented with choroidal hemorrhage and angle closure glaucoma. The second case is a 42-year-old man who presented with choroidal hemorrhage and posterior scleritis. Vitrectomy with transvitreous fine needle aspiration biopsy was ultimately required to diagnose malignant uveal melanoma in each case. CONCLUSIONS AND IMPORTANCE: Intraocular hemorrhage is a rare presenting sign of uveal melanoma. When it does occur, it is typically associated with large tumors. Hemorrhagic choroidal detachments are particularly rare in uveal melanoma, and can limit the diagnostic utility of clinical exam, B-scan ultrasonography, and magnetic resonance imaging. Although it is uncommon, it is important to maintain a high index of suspicion for choroidal melanoma in any patient with unexplained choroidal hemorrhage.

Quantitative assessment of choriocapillaris flow deficits in diabetic retinopathy: A swept-source optical coherence tomography angiography study.

PURPOSE: To quantitatively assess choriocapillaris (CC) flow deficits in eyes with diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Diabetic subjects with different stages of DR and age-matched healthy subjects were recruited and imaged with SS-OCTA. The en face CC blood flow images were generated using previously published and validated algorithms. The percentage of CC flow deficits (FD%) and the mean CC flow deficit size were calculated in a 5-mm-diameter circle centered on the fovea from the 6×6-mm scans. RESULTS: Forty-five diabetic subjects and 27 control subjects were included in the study. The CC FD% in diabetic eyes was on average 1.4-fold greater than in control eyes (12.34±4.14% vs 8.82±2.61%, P < 0.001). The mean CC FD size in diabetic eyes was on average 1.4-fold larger than in control eyes (2151.3± 650.8µm2 vs 1574.4±255.0 µm2, P < 0.001). No significant difference in CC FD% or mean CC FD size was observed between eyes with nonproliferative DR and eyes with proliferative DR (P = 1.000 and P = 1.000, respectively). CONCLUSIONS: CC perfusion in DR can be objectively and quantitatively assessed with FD% and FD size. In the macular region, both CC FD% and CC FD size are increased in eyes with DR. SS-OCTA provides new insights for the investigations of CC perfusion status in diabetes in vivo.

New developments in angiography for the diagnosis and management of diabetic retinopathy.

The most common microvascular complication of diabetes is diabetic retinopathy, the leading cause of blindness in adults of working age. Our understanding of the vascular changes in diabetic retinopathy was enhanced by the demonstration of fluorescein angiography (FA) in the human retina for the first time in 1961. It was subsequently integrated with digital fundoscopic imaging to become an invaluable technique in evaluation of the retinal vasculature. The recent development of OCT-angiography (OCT-A) has revolutionized the clinician's ability to examine the retinal vasculature without the need for injection of a contrast dye. By coupling OCT, which can provide noninvasive cross-sectional imaging of the central retina, with angiography in OCT-A, one can reveal retinal perfusion by allowing visualization of the depth-resolved retinal capillary plexus. OCT-A has allowed for more precise delineation of changes in the retinal microvasculature, specifically the alterations of retinal vasculature and loss of capillary perfusion from chronic microvascular occlusion in diabetic retinopathy.

Ultra-Widefield Protocol Enhances Automated Classification of Diabetic Retinopathy Severity with OCT Angiography.

PURPOSE: To assess the diagnostic usefulness of retinal nonperfusion to classify eyes based on diabetic retinopathy (DR) severity on OCT angiography (OCTA) and determine whether wider field of view (FOV) OCTA protocols enhance the diagnostic usefulness of retinal nonperfusion in the classification of DR severity. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Diabetic patients undergoing ultra-widefield (UWF) OCTA imaging at 1 academic retina practice. METHODS: Ultra-widefield OCTA images with 100° FOV were obtained from 60 eyes. Eyes were grouped as those with diabetes without retinopathy (DWR), those with nonproliferative diabetic retinopathy (NPDR), or those with proliferative diabetic retinopathy (PDR). The ratio of nonperfusion (RNP) was expressed as the percent area of capillary nonperfusion within the FOV. The RNP was obtained in the FOV 100° image and concentric sectors encompassing 10°, 10° to 30°, 30° to 50°, and 50° to 100°. MAIN OUTCOME MEASURES: Mean RNP among DR groups, mean RNP measured among FOV sectors, and area under the curve (AUC) of the receiver operating characteristics when using RNP as a cutoff value to distinguish between DR groups. RESULTS: Mean RNP from the FOV 50° to 100° sector was different among all groups: DWR, 14.6±5.1%; NPDR, 27.5±7.5%; and PDR, 41.5±19.1% (P < 0.01). Within each DR group, field of view from 50° to 100° measured higher RNP than all other sectors (P < 0.01). Field of view from 50° to 100° showed the highest optimal sensitivity and specificity to distinguish NPDR from DWR with an RNP cutoff value of 21.2% (89.5% and 88.2%; AUC, 0.944) and PDR from NPDR with an RNP cutoff value of 31.6% (79.2% and 78.9%; AUC, 0.752). CONCLUSIONS: Ratio of nonperfusion on average is higher in more severe DR. The most peripheral sector of the widefield OCTA (FOV 50°-100°) showed on average higher RNP and showed more diagnostic usefulness in determining DR severity compared with more central sectors and the FOV 100 image as a whole.

Retinal Capillary Nonperfusion on OCT-Angiography and Its Relationship to Kidney Function in Patients with Diabetes.

BACKGROUND: Diabetic retinopathy and kidney disease share underlying mechanisms of microvascular damage and are often comorbid in people with diabetes. We evaluated whether there is a relationship between retinal capillary perfusion as measured by swept-source optical coherence tomography angiography and estimated glomerular filtration rate (eGFR) and albuminuria in patients with diabetes and chronic kidney disease (CKD). METHOD: A cross-sectional pilot study was conducted at the University of Washington among a subset of participants with diabetes and CKD participating in a larger cohort study. Participants were excluded if they were known to have kidney disease from conditions other than diabetes. Ten participants (11 eyes) were included. Retinal nonperfusion (RNP) and vessel density (VD) were measured by swept-source optical coherence tomography angiography in 30° and 60° field of view (FOV) regions centered at the fovea. Correlations of RNP and VD with eGFR and albuminuria were analyzed. RESULTS: Participants had a mean age of 72 years, hemoglobin A1c of 8.1%, eGFR of 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio of 162 mg/g. Mean (SD) RNP was 6.6% (4.2%) and 16.9% (7.7%) in 30° and 60° FOV regions, respectively. eGFR was negatively correlated to RNP in both the 30° and 60° FOV regions (R = -0.69, p=0.004, and R = -0.46, p=0.057, respectively), and correlations were stronger among a subset of 7 participants with evidence of diabetic retinopathy on exam and fundus photos. The estimated GFR was not significantly correlated with vessel density. Urine albumin-to-creatinine ratio was not significantly correlated with RNP or VD. CONCLUSIONS: Our proof-of-concept study showed that lower eGFR was significantly correlated with retinal nonperfusion in participants with diabetes and CKD. Advanced retinal imaging may enhance the noninvasive evaluation of kidney function in diabetes.

Familial retinal arteriolar tortuosity and quantification of vascular tortuosity using swept-source optical coherence tomography angiography.

PURPOSE: Familial retinal arteriolar tortuosity (FRAT) is a rare autosomal dominant disorder that is characterized by tortuosity of the second and higher order retinal arterioles. We implement swept-source optical coherence tomography angiography (SS-OCTA) to quantify vessel tortuosity in patients with FRAT. We hypothesize that patients with FRAT will have higher retinal arteriole tortuosity when compared to controls. METHODS: Patients were scanned with a SS-OCTA device (Plex Elite 9000, Carl Zeiss Meditec, Dublin, CA). Images of a 12 × 12 mm2 area centered on the fovea were processed, and retinal vessels >23.5 µm in diameter were identified. An automatic tortuosity measurement program written in MATLAB was used to assess vessel tortuosity. Branch points in the vessels were detected and used to separate the vasculature into individual segments. The tortuosity was measured by calculating the arc-chord ratio of each vessel segment, where a minimum value of 1 indicated a straight vessel and higher values corresponded to increasing tortuosity. RESULTS: Two patients (4 eyes) with a known history of FRAT and six controls (12 eyes) were enrolled in the study. The mean tortuosity of all vessel segments (MTVS) in scans of FRAT eyes was on average 1.1244 [range: 1.1044-1.1438] while for control eyes it was 1.0818 [range: 1.0746-1.0872]. Average MTVS of FRAT eyes was significantly higher compared to control eyes (p = 0.03). CONCLUSIONS AND IMPORTANCE: Our results are consistent with the hypothesis that patients with FRAT have higher objective measurements of tortuosity compared to controls. Broader applications of this method may be of benefit in other retinal diseases with changes in retinal vessel configuration.

Ultra-wide optical coherence tomography angiography in diabetic retinopathy.

BACKGROUND: To implement an ultra-wide optical coherence tomography angiography imaging (UW-OCTA) modality in eyes with diabetic retinopathy (DR) with the aim of quantifying the burden of microvascular disease at baseline and subsequent clinic visits. METHODS: UW-OCTA was implemented on a 1,060 nm swept source (SS) OCTA engine running at 100 kHz A-line rate with a motion tracking mechanism. A montage scanning protocol was used to capture a 100-degree field of view (FOV) using a 4×4 grid of sixteen total individual 6×6 mm2 scans. Typical OCTA images with a FOV of 3×3, 6×6 and 12×12 mm2 were obtained for comparison. DR patients were scanned at baseline and follow-up. They were treated at the clinician's discretion. Vessel density and non-perfusion area maps were calculated based on the UW-OCTA images. RESULTS: Three proliferative DR patients were included in the study. UW-OCTA images provided more detailed visualization of vascular networks compared to 50-degree fluorescein angiography (FA) and showed higher burden of pathology in the retinal periphery that was not captured by typical OCTA. Neovascularization complexes were clearly detected in the two patients with active PDR. Vessel density and non-perfusion maps were used to measure progressive capillary non-perfusion and regression of neovascularization between visits. CONCLUSIONS: UW-OCTA provides approximately 100-degree OCTA images of the fundus comparable to that of wide-angle fundus photography, and may be more applicable in conditions such as DR which affect the peripheral retina in contrast to standard OCTA.

Leadership of United States Academic Departments of Ophthalmology: Chairperson Characteristics, Accomplishments, and Personal Insights.

PURPOSE: To report on the characteristics, accomplishments, and past experiences of current academic ophthalmology department chairs. DESIGN: Cross-sectional study. METHODS: Setting: A confidential online survey. STUDY POPULATION: Total of 111 chairs of US academic ophthalmology departments. MAIN OUTCOME MEASURES: Chairs' general characteristics, training/former positions held, academic accomplishments, previous organization/committee involvement, motivation/insight, and overall work satisfaction. RESULTS: Fifty-five chair responses were received (96% male, mean age 57 years, mean term 7 years). The majority were American medical graduates (93%), full professors of ophthalmology (93%), and permanent chairs (96%). All completed their residency in the US and 96% completed a fellowship (25% vitreoretinal surgery, 22% cornea and external disease, and 20% glaucoma). On average, chairs authored 98 peer-reviewed articles, 2 books, and 11 book chapters. They were also significantly involved in peer-reviewed journal literature, serving as editors (20%), associate editors (18%), or editorial board members (60%). The majority of chairs indicated they decided to seek their position late in their career, having already become a full (33%) or associate professor (26%), primarily owing to a desire to build and promote an academic ophthalmology department (61%). Chairs regarded their experience as head of service as most important for their current performance as department heads. Their principal advice to aspiring ophthalmology chairs was to focus on developing skills as a clinician, researcher, and educator ("triple threat"). CONCLUSIONS: Overall, academic department chairs are accomplished leaders in ophthalmology and prolific authors with an established academic record. Chairs regarded their previous leadership roles within the department as invaluable to their effectiveness as chair.

Chorioretinal Perfusion in Persistent Placoid Maculopathy.

Persistent placoid maculopathy (PPM) is a rare clinical entity that has previously been reported in the literature with a characteristic appearance on multimodal imaging, including hypofluorescence observed on fluorescein angiogram (FA) and indocyanine green angiography (ICGA). The leading mechanisms proposed for this hypofluorescence include impaired choroidal vasculature with nonperfusion of the choriocapillaris and/or blockage of choroidal fluorescence by inflammatory deposits. This report demonstrates previously unreported characteristics of chorioretinal perfusion in a case of acute onset PPM in a 58-year-old woman. Optical coherence tomography angiography confirmed hypoperfusion of the choriocapillaris corresponding to the hypoperfusion seen on FA and ICGA. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1026-1031.].

Bilateral Retinal Detachments After Intravitreal Injection of Adipose-Derived 'Stem Cells' in a Patient With Exudative Macular Degeneration.

A 77-year-old woman with exudative macular degeneration underwent bilateral intravitreal injections of "stem cells" at a clinic in Georgia. One month and 3 months after injection, she developed retinal detachments in the left and right eyes, respectively. Increased awareness within the medical community of such poor outcomes is critical so that clinics offering untested practices that have been shown to be potentially harmful to patients can be identified and brought under U.S. Food and Drug Administration oversight. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:772-775.].