Gene Editing for CEP290-Associated Retinal Degeneration.

BACKGROUND: CEP290-associated inherited retinal degeneration causes severe early-onset vision loss due to pathogenic variants in CEP290. EDIT-101 is a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing complex designed to treat inherited retinal degeneration caused by a specific damaging variant in intron 26 of CEP290 (IVS26 variant). METHODS: We performed a phase 1-2, open-label, single-ascending-dose study in which persons 3 years of age or older with CEP290-associated inherited retinal degeneration caused by a homozygous or compound heterozygous IVS26 variant received a subretinal injection of EDIT-101 in the worse (study) eye. The primary outcome was safety, which included adverse events and dose-limiting toxic effects. Key secondary efficacy outcomes were the change from baseline in the best corrected visual acuity, the retinal sensitivity detected with the use of full-field stimulus testing (FST), the score on the Ora-Visual Navigation Challenge mobility test, and the vision-related quality-of-life score on the National Eye Institute Visual Function Questionnaire-25 (in adults) or the Children's Visual Function Questionnaire (in children). RESULTS: EDIT-101 was injected in 12 adults 17 to 63 years of age (median, 37 years) at a low dose (in 2 participants), an intermediate dose (in 5), or a high dose (in 5) and in 2 children 9 and 14 years of age at the intermediate dose. At baseline, the median best corrected visual acuity in the study eye was 2.4 log10 of the minimum angle of resolution (range, 3.9 to 0.6). No serious adverse events related to the treatment or procedure and no dose-limiting toxic effects were recorded. Six participants had a meaningful improvement from baseline in cone-mediated vision as assessed with the use of FST, of whom 5 had improvement in at least one other key secondary outcome. Nine participants (64%) had a meaningful improvement from baseline in the best corrected visual acuity, the sensitivity to red light as measured with FST, or the score on the mobility test. Six participants had a meaningful improvement from baseline in the vision-related quality-of-life score. CONCLUSIONS: The safety profile and improvements in photoreceptor function after EDIT-101 treatment in this small phase 1-2 study support further research of in vivo CRISPR-Cas9 gene editing to treat inherited retinal degenerations due to the IVS26 variant of CEP290 and other genetic causes. (Funded by Editas Medicine and others; BRILLIANCE ClinicalTrials.gov number, NCT03872479.).

Thiophene-based lipids for mRNA delivery to pulmonary and retinal tissues.

Lipid nanoparticles (LNPs) largely rely on ionizable lipids to yield successful nucleic acid delivery via electrostatic disruption of the endosomal membrane. Here, we report the identification and evaluation of ionizable lipids containing a thiophene moiety (Thio-lipids). The Thio-lipids can be readily synthesized via the Gewald reaction, allowing for modular lipid design with functional constituents at various positions of the thiophene ring. Through the rational design of ionizable lipid structure, we prepared 47 Thio-lipids and identified some structural criteria required in Thio-lipids for efficient mRNA (messenger RNA) encapsulation and delivery in vitro and in vivo. Notably, none of the tested lipids have a pH-response profile like traditional ionizable lipids, potentially due to the electron delocalization in the thiophene core. Placement of the tails and localization of the ionizable headgroup in the thiophene core can endow the nanoparticles with the capability to reach various tissues. Using high-throughput formulation and barcoding techniques, we optimized the formulations to select two top lipids-20b and 29d-and investigated their biodistribution in mice. Lipid 20b enabled LNPs to transfect the liver and spleen, and 29d LNP transfected the lung and spleen. Unexpectedly, LNP with lipid 20b was especially potent in mRNA delivery to the retina with no acute toxicity, leading to the successful delivery to the photoreceptors and retinal pigment epithelium in non-human primates.

Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.

BACKGROUND: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1. METHODS: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study. All patients received unilateral subretinal injections of ATSN-101. In the dose-escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1·0 × 1010 vg/eye (low dose), 3·0 × 1010 vg/eye (middle dose), and 1·0 × 1011 vg/eye (high dose). In the dose-expansion phase, one adult cohort (n=3) and one paediatric cohort (n=3) were treated at the high dose. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also done. Data through the 12-month main study period are reported. FINDINGS: Patients were enrolled between Sept 12, 2019, and May 5, 2022. A total of 68 TEAEs were observed, 56 of which were related to the surgical procedure. No serious TEAE was related to the study drug. Ocular inflammation was mild and reversible with steroid treatment. For patients who received the high dose, mean change in dark-adapted FST was 20·3 decibels (dB; 95% CI 6·6 to 34·0) for treated eyes and 1·1 dB (-3·7 to 5·9) for untreated eyes at month 12 (white stimulus); improvements were first observed at day 28 and persisted over 12 months (p=0·012). Modest improvements in BCVA were also observed (p=0·10). Three of six patients who received the high dose and did the MLMT achieved the maximum score in the treated eye. INTERPRETATION: ATSN-101 is well tolerated 12 months after treatment, with no drug-related serious adverse events. Clinically significant improvements in retinal sensitivity were sustained in patients receiving the high dose. FUNDING: Atsena Therapeutics.

Preformed Vesicle Approach to LNP Manufacturing Enhances Retinal mRNA Delivery.

Complete encapsulation of nucleic acids by lipid-based nanoparticles (LNPs) is often thought to be one of the main prerequisites for successful nucleic acid delivery, as the lipid environment protects mRNA from degradation by external nucleases and assists in initiating delivery processes. However, delivery of mRNA via a preformed vesicle approach (PFV-LNPs) defies this precondition. Unlike traditional LNPs, PFV-LNPs are formed via a solvent-free mixing process, leading to a superficial mRNA localization. While demonstrating low encapsulation efficiency in the RiboGreen assay, PFV-LNPs improved delivery of mRNA to the retina by up to 50% compared to the LNP analogs across several benchmark formulations, suggesting the utility of this approach regardless of the lipid composition. Successful mRNA and gene editors' delivery is observed in the retinal pigment epithelium and photoreceptors and validated in mice, non-human primates, and human retinal organoids. Deploying PFV-LNPs in gene editing experiments result in a similar extent of gene editing compared to analogous LNP (up to 3% on genomic level) in the Ai9 reporter mouse model; but, remarkably, retinal tolerability is significantly improved for PFV-LNP treatment. The study findings indicate that the LNP formulation process can greatly influence mRNA transfection and gene editing outcomes, improving LNP treatment safety without sacrificing efficacy.

Injection pressure levels for creating blebs during subretinal gene therapy.

Retinal damage has been associated with increased injection pressure during subretinal gene therapy delivery in various animal models, yet there are no human clinical data regarding the pressures required to initiate and propagate subretinal blebs. This study characterized the intraoperative pressure levels for subretinal gene therapy delivery across eight retinal conditions. A total of 116 patients with retinal degenerative diseases have been treated with subretinal gene therapy at OHSU-Casey Eye Institute as of June 2020; seventy patients (60.3%) were treated using a pneumatic-assisted subretinal delivery system. All retinal blebs were performed using a 41-gauge injection cannula, and use of a balanced salt solution (BSS) "pre-bleb" prior to gene therapy delivery was performed at the discretion of the surgeon. Patient age and intraoperative data for BSS and vector injections were analyzed in a masked fashion for all patients who received pneumatic-assisted subretinal gene therapy. The median age of the patients was 35 years (range 4-70). No significant differences in injection pressures were found across the eight retinal conditions. In this study, patient age was shown to affect maximum injection pressures required for bleb propagation, and the relationship between age and pressure varied based on retinal condition. These data have important implications in optimizing surgical protocols for subretinal injections.

Gordonia bronchialis-Associated Endophthalmitis, Oregon, USA.

Gordonia bronchialis is an aerobic actinomycetes that rarely causes infections in humans. Few reports describe Gordonia spp. causing eye-related infections. We report a case of chronic infectious endophthalmitis in Oregon, USA, associated with infection by G. bronchialis.

Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye.

Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.

CLINICOPATHOLOGIC CORRELATION OF RETINAL ANGIOMATOUS PROLIFERATION TREATED WITH RANIBIZUMAB.

PURPOSE: To describe histopathologic features of an eye with retinal angiomatous proliferation (RAP) secondary to age-related macular degeneration treated with serial ranibizumab injections and to correlate these findings with spectral domain optical coherence tomography. METHODS: Histopathologic features from serial sections through the globe of a 93-year-old man with age-related macular degeneration were studied and compared with spectral domain optical coherence tomography images obtained 7 weeks before his death. RESULTS: The pathologic correlate of ranibizumab-treated RAP was a circumscribed, branching paucicellular vascular complex extending from the inner plexiform layer to Bruch membrane. The histopathologic findings corresponded to an area of hyperreflectivity on spectral domain optical coherence tomography imaging, substantiating the reported tomographic appearance of RAP lesions. A frank anastomosis with choroidal or retinal vasculature was not seen in this treated RAP lesion. There was a lack of retinal pigment epithelium underlying the lesion in an area of retinal pigment epithelium detachment. The elastic portion of Bruch membrane appeared intact. Treatment with ranibizumab over an extended period of time may have been associated with a loss of cellularity of the RAP lesion. CONCLUSION: In a patient with ARMD extensively treated with ranibizumab, color fundus photography, fluorescein angiography and SD-OCT images of RAP correlated histopathologically with a paucicellular intraretinal vascular complex.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF DIABETIC RETINOPATHY.

PURPOSE: To describe the optical coherence tomography angiography features of diabetic retinopathy. METHODS: Using a 70 kHz optical coherence tomography and the split-spectrum amplitude decorrelation angiography algorithm, 6 mm × 6 mm 3-dimensional angiograms of the macula of 4 patients with diabetic retinopathy were obtained and compared with fluorescein angiography for features cataloged by the Early Treatment of Diabetic Retinopathy Study. RESULTS: Optical coherence tomography angiography detected enlargement and distortion of the foveal avascular zone, retinal capillary dropout, and pruning of arteriolar branches. Areas of capillary loss obscured by fluorescein leakage on fluorescein angiography were more clearly defined on optical coherence tomography angiography. Some areas of focal leakage on fluorescein angiography that were thought to be microaneurysms were found to be small tufts of neovascularization that extended above the inner limiting membrane. CONCLUSION: Optical coherence tomography angiography does not show leakage but can better delineate areas of capillary dropout and detect early retinal neovascularization. This new noninvasive angiography technology may be useful for routine surveillance of proliferative and ischemic changes in diabetic retinopathy.

DETECTION OF NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate eyes with age-related macular degeneration and high-risk characteristics for choroidal neovascularization (CNV) with optical coherence tomographic (OCT) angiography to determine whether earlier detection of CNV is possible. METHODS: Eyes with drusen, pigmentary changes, and with CNV in the fellow eye were scanned with a 70-kHz spectral domain OCT system (Optovue RTVue-XR Avanti). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. Two masked graders reviewed scans for CNV, defined as flow in the outer retinal/sub-RPE slab. Choroidal neovascularization flow area repeatability and between-grader reproducibility were calculated. RESULTS: Of 32 eyes, 2 (6%) were found to have Type 1 CNV with OCT angiography. The lesions were not associated with leakage on fluorescein angiography or fluid on OCT. One case was followed for 8 months without treatment, and the CNV flow area enlarged slightly without fluid buildup on OCT or vision loss. Between-grader reproducibility of the CNV flow area was 9.4% (coefficient of variation) and within-visit repeatability was 5.2% (pooled coefficient of variation). CONCLUSION: Optical coherence tomographic angiography can detect the presence of nonexudative CNV, lesions difficult to identify with fluorescein angiography and OCT. Further study is needed to understand the significance and natural history of these lesions.

Polypoidal choroidal vasculopathy in white patients.

PURPOSE: To report on a series of white patients in the United States with polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective chart review of 27 patients at a single center with PCV. RESULTS: The mean age was 74.3 with 48% being male. The most common presenting diagnosis was exudative age-related macular degeneration in 59%, and it took 17.5 months to diagnose PCV. During this time, patients received one antivascular endothelial growth factor injection every 1.3 months. The most common reason for suspecting PCV was a large retinal pigment epithelial detachment or a poor response to antivascular endothelial growth factor therapy. Once PCV was diagnosed, most underwent photodynamic therapy. In those who received photodynamic therapy, the fluid and/or age-related macular degeneration decreased in 86%. The vision improved in 41% with 36% maintaining stable vision. Patients received only one additional injection every 3.95 months after photodynamic therapy. CONCLUSION: This is one of the larger series of PCV in an entirely white population. It emphasizes the importance of diagnosis in whites as PCV can masquerade as recalcitrant exudative age-related macular degeneration. Common findings were a temporal or peripapillary location and the presence of lipid. After photodynamic therapy, the patients still required antivascular endothelial growth factor therapy, but the injection burden was decreased by 67% and vision was found to be improved or maintained in 77% of patients.

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.

Purpose: To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Design: Single-center, retrospective chart review. Methods: In this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Results: Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. Conclusions: We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Translational Relevance: Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

Foveal involvement by acquired retinoschisis: long-term visual outcomes.

PURPOSE: To report the long-term findings of acquired retinoschisis whose posterior border was <10° from the fovea. METHODS: Retrospective case series. RESULTS: Over a 43-year period, 2 patients retained central vision when the foveola was involved by retinoschisis alone. In these two and in another four patients, the development of outer layer holes eventually was followed by either outer layer or full thickness retinal detachment into the foveola with loss of central vision. Laser treatment or vitrectomy prevented this in three patients. A seventh patient is being monitored by periodic spectral domain optical computerized tomography. CONCLUSION: Acquired retinoschisis that progress into the foveola without an outer layer detachment is compatible with preservation of some degree of central vision. If an outer layer detachment develops under the foveola, such patients lose central vision. Periodic monitoring by spectral domain optical computerized tomography should help to avoid or detect this complication.

The retina-brain axis and diabetic retinopathy.

Diabetic retinopathy (DR) is a major contributor to permanent vision loss and blindness. Changes in retinal neurons, glia, and microvasculature have been the focus of intensive study in the quest to better understand DR. However, the impact of diabetes on the rest of the visual system has received less attention. There are reports of associations of changes in the visual system with preclinical and clinical manifestations of diabetes. Simultaneous investigation of the retina and the brain may shed light on the mechanisms underlying neurodegeneration in diabetics. Additionally, investigating the links between DR and other neurodegenerative disorders of the brain including Alzheimer's and Parkinson's disease may reveal shared mechanisms for neurodegeneration and potential therapy options.

Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates.

Lipid nanoparticle (LNP)-based mRNA delivery holds promise for the treatment of inherited retinal degenerations. Currently, LNP-mediated mRNA delivery is restricted to the retinal pigment epithelium (RPE) and Müller glia. LNPs must overcome ocular barriers to transfect neuronal cells critical for visual phototransduction, the photoreceptors (PRs). We used a combinatorial M13 bacteriophage-based heptameric peptide phage display library for the mining of peptide ligands that target PRs. We identified the most promising peptide candidates resulting from in vivo biopanning. Dye-conjugated peptides showed rapid localization to the PRs. LNPs decorated with the top-performing peptide ligands delivered mRNA to the PRs, RPE, and Müller glia in mice. This distribution translated to the nonhuman primate eye, wherein robust protein expression was observed in the PRs, Müller glia, and RPE. Overall, we have developed peptide-conjugated LNPs that can enable mRNA delivery to the neural retina, expanding the utility of LNP-mRNA therapies for inherited blindness.

Improved Rod Sensitivity as Assessed by Two-Color Dark-Adapted Perimetry in Patients With RPE65-Related Retinopathy Treated With Voretigene Neparvovec-rzyl.

Purpose: The purpose of this study was to evaluate rod-mediated function with two-color dark-adapted perimetry (2cDAP) in patients with RPE65-related retinopathy treated with voretigene neparvovec-rzyl. Methods: Following dilation and dark adaptation, 2cDAP and FST were performed. The 2cDAP was measured on an Octopus 900 perimeter (Haag-Streit) with cyan (500 nm wavelength) and red (650 nm wavelength) stimuli. Hill of vision (HOV) analysis was performed on 2cDAP perimetry with Visual Field Modeling and Analysis (VFMA). Full field threshold stimulus testing (FST) was also measured as a secondary measure of rod-mediated function, and assessed on a Diagnosys Espion with the ColorDome stimulator (Diagnosys LLC). Results: Eight eyes from 4 patients who were treated with voretigene bilaterally had rod function assessed by 2cDAP testing at least 1 year after treatment. There was statistically significant improvement in 2cDAP following gene augmentation therapy. HOV VFMA analysis showed widespread improvements that extended beyond the treatment bleb and statistically significant improvement in HOV analysis volumetric measurements post-treatment to cyan and red stimuli. FST testing performed in six eyes from three patients demonstrated statistically significant improvement to all chromatic stimuli following treatment. Conclusions: These findings demonstrated statistically significant improvement in 2cDAP and FST following treatment with voretigene. Translational Relevance: These findings provide a sensitive method of assessing rod-mediated function in a topographic manner that may be useful in future clinical trials for inherited retinal dystrophies.

A multicenter analysis of the ophthalmic knowledge assessment program and American Board of Ophthalmology written qualifying examination performance.

OBJECTIVE: To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs. DESIGN: Comparative case series. PARTICIPANTS: Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available. METHODS: Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE. MAIN OUTCOME MEASURES: The primary outcome measure of this study was first time pass rate for the WQE. RESULTS: Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher. CONCLUSIONS: The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination.

Iatrogenic choroidal neovascularization associated with subretinal gene therapy surgery.

Purpose: To report a case of iatrogenic choroidal neovascularization (CNV) developing one month after subretinal gene therapy surgery. Observations: A 16-year-old male with biallelic RPE65 mutation associated retinal dystrophy was treated with subretinal voretigene neparvovec in the left eye. During initiation of a balanced salt solution pre-bleb, a faint and transient subretinal hemorrhage was observed at the retinotomy site. One month post-operatively, multi-modal imaging detected a CNV and a break in Bruch's membrane at the retinotomy site. The asymptomatic CNV was observed without treatment and resolved spontaneously. Conclusions & importance: As subretinal gene therapy surgery becomes more common, clinicians should monitor for possible trauma induced CNV associated with retinotomy formation and subretinal injection.

Trends in Ophthalmology Resident Operative Experience and the Early Impact of the COVID-19 Pandemic.

Purpose This study aimed to evaluate trends in ophthalmology resident operative experience and the early impact of the novel coronavirus disease 2019 (COVID-19) pandemic. Design Present study is a retrospective analysis of the Accreditation Council for Graduate Medical Education (ACGME) Case Log System. Participants Anonymized graduating resident case logs from 2011 to 2020 academic years (AYs) were examined for this study. Methods Regression analysis for each procedure category was performed to identify trends between 2011 and 2019 AYs. Unpaired two-tailed t -test compared 2018 to 2019 and 2019 to 2020 AY's for each category surgeon (S) and as surgeon and assistant (S + A). Main Outcome Measures Mean and median cases as (S) and (S + A) during 2011 to 2019 AYs. Comparison between 2018 to 2019 and 2019 to 2020 AY's for each category as (S) and (S + A) to evaluate the impact of the COVID-19 pandemic. Results Total ophthalmology procedures as (S) rose from a mean of 479.6 to 601.3 ( p < 0.001; R 2 = 0.96; Δ/year = 16.9) and a median of 444 to 537 ( p < 0.001; R 2 = 0.97; Δ/year = 13.1). Total procedures as (S + A) rose from a mean of 698.1 to 768 ( p < 0.01; R 2 = 0.83; Δ/year = 9.07) and a median of 677 to 734 ( p < 0.05; R 2 = 0.61; Δ/year = 6.64). Cataract procedures as (S) rose from a mean of 152.8 to 208 ( p < 0.001; R 2 = 0.99; Δ/year = 7.98) and a median of 146 to 197 ( p < 0.001; R 2 = 0.97; Δ/year = 7.87). Cataract procedures as both (S + A) rose from a mean 231.4 to 268.7 ( p < 0.001; R 2 = 0.95; Δ/year = 5.5) and a median of 213 to 254 ( p < 0.001; R 2 = 0.93; Δ/year = 5.33). Between 2018 to 2019 and 2019 to 2020 AYs, the first pandemic year was associated with significant reductions in total procedures (601.3-533.7 [ p < 0.0001]) as (S) and 768.0 to 694.4 ( p < 0.0001) as (S + A), cataract surgery (208-162.2 [ p < 0.0001]) as (S) and 268.7 to 219.1 ( p < 0.0001) as (S + A), and glaucoma surgery (16.3-14.2 [ p = 0.0068]) as (S) and 25.6 to 22.6 ( p = 0.0063) as (S + A). Conclusion During 2011 to 2019 AYs, cataract, intravitreal injections, glaucoma, and total procedures increased significantly. During the early period of the COVID-19 pandemic (2019-2020 AY), national halting of elective procedures had a precipitous effect on resident cataract surgery experience to volumes similar to 2013 to 2014 AY where the mean was twice the current required minimum number. With few exceptions, other procedure volumes remained stable.

Prospective evaluation of optical coherence tomography for disease detection in the Casey mobile eye clinic.

This study was designed to evaluate iVue Spectral-domain optical coherence tomography (SD-OCT) effectiveness in screening for eye disease compared to clinical examination. Subjects were recruited from the Casey Eye Community Outreach Program Mobile Clinic during its routinely scheduled outreach clinics to indigent, underserved populations throughout Oregon. Macular optical coherence tomography interpretation and automated optical coherence tomography analysis were compared to the clinical examination, with specific attention to findings indicative of retinal abnormalities, risks for glaucoma, and narrow angles. As a result, a total of 114 subjects were included in this study. In diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.39), with 22% of eyes having abnormal findings on macular optical coherence tomography and 26% of eyes having diabetic retinopathy or diabetic macular edema on fundus exam. In non-diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.28), with 11% of eyes having abnormal findings on macular optical coherence tomography and 9% on fundus exam. Using optical coherence tomography ganglion cell complex and retinal nerve fiber layer analysis, 18% of eyes were found to be glaucoma suspects, whereas clinical exam of cup-to-disc ratio detected 8% and intraocular pressure 5%. Agreements between optical coherence tomography and other methods were poor (kappa < 0.11) for glaucoma suspect. Anterior segment optical coherence tomography of the angle found 8% of eyes to have occludable angles, whereas slit lamp and gonioscopy found 5% of eyes to have narrow angles, with moderate agreement (kappa = 0.57). In summary, optical coherence tomography detected additional retinal abnormalities, glaucoma suspects, and narrow angles compared to clinical exam alone and may serve as a useful adjunct to the clinical exam in screening for eye disease in a low-risk, medically underserved, ethnically diverse population.