Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography.

BACKGROUND: Automated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans. METHODS: In this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman's correlation was run to examine if the algorithm's probability score was associated with the severity stages of IFTMH. RESULTS: Six hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman's correlation coefficient of 0.15 was achieved between the algorithm's probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied. CONCLUSIONS: The DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm's probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Perioperative COVID-19 Screening at a Tertiary Ophthalmic Institution.

Purpose: To characterize the rate of COVID-19 positivity during presurgical screening and the surgical outcomes of ophthalmic patients who were positive for COVID-19 and to report the overall cost. Methods: This retrospective study included patients 18 years or older who had ophthalmic surgical procedures at a tertiary institution between May 11, 2020, and December 31, 2020. Patients without a valid presurgical COVID-19 test within 3 days before their scheduled procedure, who had incomplete or mislabeled visits, or who had incomplete or missing data in their file were excluded. COVID-19 screening was completed using a polymerase chain reaction (PCR) kit. Results: Of the 3585 patients who met the inclusion criteria, 2044 (57.02%) were women; the mean age was 68.2 years ± 12.8 (SD). Thirteen asymptomatic patients (0.36%) tested positive for COVID-19 via PCR screening. Three patients had a known positive COVID-19 infection within the 90 days before surgery; thus, 10 patients (0.28%) were found to have asymptomatic naïve COVID-19 infection via PCR testing. Testing was associated with a total charge of US $800 000. Five of the 13 patients (38.46%) who tested positive for COVID-19 experienced a delay in their surgery; the mean delay was 17.23 ± 22.97 days. Conclusions: Asymptomatic ophthalmic surgical patients had a low positivity rate with a limited impact on surgery scheduling at a significant cost. Further studies would be valuable in evaluating a targeted presurgical screening population as opposed to universal testing.

Baseline factors and reason for cancellation of elective ophthalmic surgery.

OBJECTIVES: To determine the baseline risk factors for elective ophthalmic surgery cancellations and characterise the reasons for cancellation. METHODS: This is a retrospective, non-randomised study performed at a large tertiary ophthalmic centre. It included a consecutive sample of patients above the age of 18 who had an ophthalmic surgery scheduled at Cole Eye Institute, Cleveland Clinic, OH between January 2012 and December 2019. An automated search pull identified 75,908 scheduled surgeries (63,987 completed and 11,921 cancelled surgeries). Statistical analysis was performed using R (version 3.5.1). Main outcome measures were baseline factors that impact risk for surgery cancellation and reasons for surgery cancellation. RESULTS: Analysis was performed on 69,963 scheduled surgeries (57.37% Female, 42.63% Male; Mean age of 62.72 years; 59,959 completed and 10,004 cancelled surgeries). Of the 2384 cancelled surgeries with reasons provided, the most common causes of cancellation were patient refusal (38.42%), patient health condition (18.79%), and rescheduling of surgery (15.27%). Female sex, black race, patient age less than 50 years, non-cataract surgeries, regional mean household income greater than $82,900, Medicare insurance, and geographical distance of less than 10 miles from home to the surgery site were each associated with a significantly increased risk of surgery cancellation (p < 0.01). CONCLUSIONS: This study successfully identified several baseline factors predicting elective ophthalmic surgery cancellation. The clinical insights gained from these lines of enquiry may be used to construct models that not only identify patients at greater risk for cancellation but also highlight which interventions have greatest efficacy in preventing ophthalmic surgery cancellations.

Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence.

PURPOSE: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. METHODS: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. RESULTS: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity (P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity (P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity (P = 0.018 and 0.024, respectively). CONCLUSIONS: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.].

Characterization of ophthalmology virtual visits during the COVID-19 pandemic.

OBJECTIVES: To characterize the use of virtual visits, as well as compare the characteristics to in-person visits during the pandemic period. METHODS: This retrospective study included patients who had virtual and in-person ophthalmology visits from March 19, 2020, to July 31, 2020, in a large multispecialty ophthalmic center. Exclusion criteria included patients aged less than 18 years old; canceled, incomplete, mislabelled, and duplicated visits. 2943 virtual and 56,174 in-person visits were identified. A random sample of 3000 in-person visits was created. Each visit was analyzed as an individual data point. RESULTS: 2,266 virtual visits (2,049 patients, 64.3% female, mean [SD] age 64.3 [16.6] years old) and 2590 in-person visits (2509 patients, 59.5% female, 65.9 [15.8] years old) were included. Most virtual visits were classified as comprehensive ophthalmology (34.6%), optometry-related (19.5%), and oculoplastics (13.0%). For in-person visits, the most common specialties were optometry (29.8%), comprehensive ophthalmology (23.9%), and retina and uveitis (17.3%). The most common diagnoses in the virtual group were from the eyelids, lacrimal system, and orbits group (26.9%), while in the in-person groups were choroid and retina conditions (19.3%). CONCLUSIONS: Numerous ocular conditions were evaluated and managed through virtual visits, and external complaints and oculoplastic consults appear to be well-suited to the virtual format. Further studies focusing on visual outcomes and patient experience will be beneficial.

Impact of retinal fluid in patients with diabetic macular edema treated with anti-VEGF in routine clinical practice.

OBJECTIVE: This study aims to determine the effect of intraretinal (IRF) and subretinal (SRF) fluid on visual outcomes for diabetic macular edema (DME) patients treated with anti-vascular endothelial growth factor (anti-VEGF) in routine clinical practice. DESIGN: Optical coherence tomography scans were analyzed with a deep-learning artificial intelligence software to quantify IRF, SRF, and total retinal fluid (TRF) at baseline and at 3, 6, and 12 months. Predictive variables for best-corrected visual acuity (BCVA) were evaluated with linear mixed-effects regression models. PARTICIPANTS: A total of 220 DME eyes of 220 patients from the Cole Eye Institute at Cleveland Clinic. METHODS: Retrospective, nonrandomized cohort study. RESULTS: BCVA improved from baseline to 12 months (63.36 ± 14.72 to 68.49 ± 13.14 Early Treatment Diabetic Retinopathy Study letters, p < 0.001, respectively). Central subfield thickness improved from baseline to 12 months (411.74 ± 129.7 to 335.94 ± 116.91 mm, p < 0.001, respectively). Injection frequency per patient was 8.25 ± 2.5 injections over 12 months. The linear mixed-effects regression model in the foveal region for TRF, IRF, and SRF volume at the fourth quartile showed BCVA losses of -8.29 letters (range, -10.96 to -5.62 letters, p < 0.001), -7.52 letters (range, -10.3 to -4.74 letters, p < .001), and -6.93 letters (range, -10.54 to -3.41 letters, p < .001), respectively. CONCLUSIONS: The highest quartile of TRF, IRF, and SRF volumes led to worse visual outcomes after 12 months of anti-VEGF treatment in patients with DME. Further studies designed to investigate the effect of anti-VEGF treatment on retinal fluid morphology could provide greater insight into individualized DME treatment.

Opioid Prescription in Ophthalmology and the Impact of a Decision Support Tool in Reducing Excess Dosing.

PURPOSE: To characterize opioid prescribing in ophthalmology and to determine the impact of an alert system on opioid prescription patterns. DESIGN: Retrospective pre- and post-implementation study. METHODS: The study population included individuals aged ≥18 years who received opioids written by ophthalmologists within a tertiary care center between January 3, 2015, and November 3, 2021, in the context of an opioid alert system. Mean morphine equivalent daily dose (MEDD) per prescription was compared before and after implementation of the opioid alert system. Additionally, mean MEDD per prescription was compared based on patient demographics and diagnoses. RESULTS: A total of 8014 individual patients were included in this study. The study population received a total of 9055 prescriptions, 77% of which were written for pain management related to an ophthalmic surgery. Mean MEDD per prescription decreased by 15.17 after implementation of the alert system (P < .001). A higher mean MEDD per prescription was observed among males (33.53 MEDD; P < .001). Black individuals received a higher mean MEDD per prescription (33.93 MEDD) compared with white individuals (32.80 MEDD; P = .03). Opioids written for disorders of the eyelid, lacrimal system, and orbit constituted 57.4% of total prescriptions. CONCLUSIONS: Prescription patterns based on patient demographics and diagnoses can provide foci for opioid prescription reform in ophthalmology. The observed decrease in opioid dosage may indicate realization of the alert system.

Impact of Persistent Retinal Fluid in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: To determine whether quantification of intraretinal fluid (IRF) and subretinal fluid (SRF) can be used as a biomarker for predicting visual prognosis in routine clinical practice. PATIENTS AND METHODS: Retrospective, nonrandomized cohort study review of patients with neovascular age-related macular degeneration from January 1, 2012, to March 1, 2018. RESULTS: In the 286-patient cohort, the mean baseline, 6-month, and 12-month best-corrected visual acuity (BCVA) was 60.24 ± 18.63, 65.57 ± 16.56, and 65.61 ± 17.37 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively (P < .001). The regression coefficient in the linear mixed effects regression model quantifying the association between eyes in the fourth and first quartile of IRF and 12-month BCVA was -4.14 (95% CI, -6.65 to -1.63) (P = .001) ETDRS letters. The regression coefficient quantifying the association between eyes in the fourth and first quartile of SRF and 12-month BCVA was -0.7 (95% CI, -3.07 to 1.27) (P = .56) ETDRS letters. CONCLUSION: IRF and SRF are valuable biomarkers for BCVA outcomes in treatment-naïve neovascular age-related macular degeneration in routine clinical practice. [Ophthalmic Surg Lasers Imaging 2022;53:317-324.].

Impact of an Electronic Decision Support Tool to Improve Ophthalmic Safety in Hydroxychloroquine Prescribing Practices.

BACKGROUND AND OBJECTIVE: The purpose of this study was to implement a clinical decision support tool (CDS) and assess its impact on adherence to 2016 American Academy of Ophthalmology (AAO) hydroxychloroquine dosing recommendations. PATIENTS AND METHODS: This retrospective, interventional study implemented an automated alert to calculate maximum daily hydroxychloroquine dose based on 2016 AAO recommendations and flag noncompliant orders. Prevalence of excessive dosing after CDS implementation was assessed. RESULTS: A total of 7,417 patients met inclusion criteria. After intervention, prevalence of excessive dosing decreased from 27.4% to 21.1% (P < .001) among all prescriptions and from 26.8% to 16.2% (P < .001) among new prescriptions. Daily doses exceeding 400 mg decreased from 0.8% to 0.02% (P < .001). Risk factors for excessive dosing included low weight (odds ratio, 75.6 [95% CI, 54.0 to 105.8]) and nonrheumatologist prescriber (odds ratio, 1.60 to 3.63; all P < .005). CONCLUSIONS: This study highlights the efficacy of a CDS in reducing excessive hydroxychloroquine dosing and improving adherence to AAO ophthalmic safety guidelines. [Ophthalmic Surg Lasers Imaging 2022;53:310-316.].

The Quantification and Impact of Persistent Retinal Fluid Compartments on Best-Corrected Visual Acuity of Patients With Retinal Vein Occlusion.

BACKGROUND AND OBJECTIVES: To evaluate the impact of persistent intraretinal fluid (IRF) and subretinal fluid (SRF) on best visual acuity (BVA) of patients with retinal vein occlusions (RVOs). PATIENTS AND METHODS: This retrospective cohort study observed 92 treatment-naïve patients with RVO during 12 months of treatment with anti-vascular endothelial growth factor agents. Deep learning was used to quantify IRF and SRF volumes, and linear mixed effects regression modeled the impact on BVA. RESULTS: Average IRF volume declined -923.1 ± 2,382.5 nL from baseline to 12 months (P < .001). Average SRF volume declined -35.4 ± 223.4 nL from baseline to 12 months (P = .139). linear mixed effects regression modeling disclosed IRF≥ 1,616 nL at all time points predicted a -10.38 letter loss at 12 months (95% CI, -14.58 to -5.9 letters; P < .001). A similar relationship was not found for SRF. CONCLUSION: Persistent IRF may be an important prognostic biomarker for BVA outcomes in real-world patients with RVO. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:139-147.].

Performance of a Machine-Learning Computational Image Analysis Algorithm in Retinal Fluid Quantification for Patients With Diabetic Macular Edema and Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: The objective is to validate an automated artificial intelligence model in detecting and quantifying fluid in diabetic macular edema (DME) and retinal vein occlusion (RVO) optical coherence tomography images. PATIENTS AND METHODS: DME (n = 100) and RVO (n = 100) images of adult patients were reviewed. The performance of machine-learning (ML) computational image analysis algorithm was evaluated against consensus manual grading. Main outcomes were accuracy and sensitivity for detection and Pearson's correlation coefficients for quantification. RESULTS: The ML algorithm had a high accuracy and sensitivity in both DME (intraretinal fluid [IRF]: 0.92, 0.97; subretinal fluid [SRF]: 0.93, 1.00) and RVO (IRF: 0.94, 0.99; SRF: 0.93, 1.00). It had moderate-high correlation in quantifying fluid in DME (total retinal fluid: 0.88; IRF: 0.88; SRF: 0.97) and RVO (total retinal fluid: 0.83; IRF: 0.76; SRF: 0.64). CONCLUSION: The ML algorithm is highly accurate and sensitive in detecting fluid in DME and RVO optical coherence tomography images and effectively quantifies IRF and SRF in both disease states, particularly in images with low to moderate fluid burden. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:123-131.].

Ocular occupational injuries in the United States between 2011-2018.

BACKGROUND: Current advocacy literature in occupational eye injury focuses on demographics and industries with the largest number of injuries. Additional demographics may also benefit from targeted advocacy that experience a greater proportion of eye injuries relative to all other occupational injuries. AIMS: To characterize which demographic groups are experiencing occupational ocular injuries in the United States. METHODS: This cross-sectional study examined de-identified individuals who experienced ocular workplace injuries from 2011 to 2018 and were reported to the survey of occupational injuries and illnesses (SOII). Data were stratified and analysed based on SOII reported characteristics. RESULTS: 197 160 out of 9 197 350 (2%) ocular workplace injuries were reported. 152 940 (78%) injuries occurred in males. Relative to all workplace injuries experienced by industry, farming, fishing and forestry saw the highest percentage of ocular injuries (6%), followed by production, and installation (4%), maintenance and repairs (4%). Employers cited contact with objects (65%) and exposure to harmful substances (26%) as leading reasons for eye injury. Relative to all injuries, chemicals frequently injured the eye (27%). CONCLUSIONS: A disproportionate number of American ocular workplace injuries occur in males who are likely relatively young. Industries such as fishing, farming and forestry see a high frequency of ocular injury relative to all occupational injuries. Hispanics see a slight increase in ocular occupational injury relative to other injuries. Advocates of occupational ocular safety should consider expanding their targeted audiences to include individuals who are part of demographics and occupations that more frequently experience an ocular workplace injury relative to all injuries.

A Review of Surgical Techniques for the Treatment of Large Idiopathic Macular Holes.

BACKGROUND AND OBJECTIVE: This meta-analysis reviews available surgical techniques for the repair of macular holes (MHs) >650 µm. MATERIAL AND METHODS: PubMed search criteria were used to identify 17 studies outlining surgical techniques for the repair of MHs >650 µm. Thirteen of the studies identified individual cases and were further analyzed based on MH classification. Success was defined as functional improvement and anatomic closure of the hole. RESULTS: Two hundred and six MHs were included in this study. There were clinically significant differences between the repair of primary and refractory MHs. Autologous retinal transplant resulted in a visual acuity improvement of -0.48 ± 0.36 log-MAR, whereas an inverted internal limiting membrane (ILM) flap and pedicle ILM flap resulted in visual acuity improvements of -0.15 ± 0.17 and -0.14 ± 0.91 logMAR, respectively. CONCLUSION: An inverted or pedicle ILM flap appears more effective for primary MHs, whereas refractory MHs benefit from a free flap. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:52-61.].

Macular thickness fluctuation in neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor.

OBJECTIVE: To establish whether increased variability in macular thickness in neovascular age-related macular degeneration (nAMD) patients affects visual outcomes in clinical practice DESIGN: Retrospective cohort study PARTICIPANTS: Treatment-naive nAMD patients studied over 24 months METHODS: Central subfield thickness (CST) values from optical coherence tomography were collected quarterly from baseline to 24 months, and standard deviations (SDs) were calculated. The relationship was modeled with mixed-effects regression between CST SD and 24-month change in visual acuity (VA). Linear regression modeling determined predictors of CST SD. RESULTS: A total of 422 eyes with nAMD were studied. Baseline and 24-month CST values (mean ± SD) were 331.2 ± 97.6 and 253.4 ± 53.6 µm (Δ = -77.8 ± 104.7 µm, p < 0.001), with CST SD across 24 months of 42.0 ± 32.8 µm. Baseline and 24-month VA were 58.8 ± 19.2 and 62.4 ± 20.6 Early Treatment of Diabetic Retinopathy Study letters (Δ = +3.7 ± 20.8 letters, p = 0.008). CST SD over 24 months was a statistically significant negative predictor of 24-month change in VA (-15.41 [-20.98, -9.83] letters per 100 µm, p < 0.001). Quartile analysis of 24-month VA by CST SD showed a +11.2-letter difference between the first and last quartiles (p < 0.001). Baseline CST was a predictor of 24-month CST SD (24.88 [22.69, 27.06] µm per 100 µm, p < 0.001). CONCLUSIONS: Higher macular thickness fluctuations are related to poorer visual outcomes at 24 months in patients with nAMD treated with anti-vascular endothelial growth factor injections. Macular thickness variability may be an important prognostic factor of visual outcomes in nAMD eyes.

Photobiomodulation therapy in age-related macular degeneration.

PURPOSE OF REVIEW: To review the available data supporting the use of photobiomodulation therapy (PBT) in the treatment of age-related macular degeneration (AMD). RECENT FINDINGS: PBT might be used in treating nonexudative AMD. Limited evidence suggests that exudative AMD may also benefit from PBT. SUMMARY: The optimal device would deliver doses of 60 J/cm2 or more with a multiwavelength composition through the pupil over short treatment intervals. Safe upper limits have not been established. More studies are needed to evaluate the efficacy of PBT in treating exudative and nonexudative AMD.

Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.

Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss in neurons led to defects in neurite stability and migration. The αN-catenin paralog, αE-catenin, acts as a switch regulating the balance between ß-catenin and Arp2/3 actin filament activities1. Loss of αN-catenin did not affect ß-catenin signaling, but recombinant αN-catenin interacted with purified actin and repressed ARP2/3 actin-branching activity. The actin-binding domain of αN-catenin or ARP2/3 inhibitors rescued the neuronal phenotype associated with CTNNA2 loss, suggesting ARP2/3 de-repression as a potential disease mechanism. Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.