Measuring Geographic Atrophy Area Using Column-Based Machine Learning Software on Spectral-Domain Optical Coherence Tomography versus Fundus Auto Fluorescence.

BACKGROUND: The purpose of this study was to compare geographic atrophy (GA) area semi-automatic measurement using fundus autofluorescence (FAF) versus optical coherence tomography (OCT) annotation with the cRORA (complete retinal pigment epithelium and outer retinal atrophy) criteria. METHODS: GA findings on FAF and OCT were semi-automatically annotated at a single time point in 36 pairs of FAF and OCT scans obtained from 36 eyes in 24 patients with dry age-related macular degeneration (AMD). The GA area, focality, perimeter, circularity, minimum and maximum Feret diameter, and minimum distance from the center were compared between FAF and OCT annotations. RESULTS: The total GA area measured on OCT was 4.74 ± 3.80 mm2. In contrast, the total GA measured on FAF was 13.47 ± 8.64 mm2 (p < 0.0001), with a mean difference of 8.72 ± 6.35 mm2. Multivariate regression analysis revealed a significant correlation between the difference in area between OCT and FAF and the total baseline lesion perimeter and maximal lesion diameter measured on OCT (adjusted r2: 0.52; p < 0.0001) and the total baseline lesion area measured on FAF (adjusted r2: 0.83; p < 0.0001). CONCLUSIONS: We report that the GA area measured on FAF differs significantly from the GA area measured on OCT. Further research is warranted in order to determine the clinical relevance of these findings.

Body mass index and astigmatism: A nationwide study.

BACKGROUND: Existing research on the relationship between body mass index (BMI) and astigmatism yields inconsistent results. This study analyses this association in a nationally representative sample of adolescents. METHODS: This retrospective, cross-sectional study included Israeli adolescents who underwent medical assessments before mandatory military service between 2011 and 2022. BMI was categorised based on the US age- and sex-matched percentiles. Astigmatism was categorised by magnitude [low-moderate: 0.75 to <3.00 diopters (D), high: ≥3.00 D], and axis orientation [with-the-rule (WTR), against-the-rule (ATR), or oblique (OBL)]. Sex-stratified regression models adjusted for sociodemographic variables were used. RESULTS: Of 935 989 adolescents evaluated, 887 325 were included [511 465 (57.6%) males, mean age 17.2 years]. Astigmatism was diagnosed in 123 675 (13.9%) adolescents, of whom 117 081 (13.2%) had low-moderate and 6594 (0.7%) had high astigmatism. WTR astigmatism was the most prevalent (8.2%), followed by ATR (4.1%) and OBL (1.6%) types. Compared with low-normal BMI (5th to 50th percentile), the adjusted ORs for total astigmatism increased with increasing BMI, peaking at 1.65 (1.57-1.74) in males and 1.74 (1.64-1.86) in females with severe obesity. ORs were accentuated for high astigmatism, reaching 3.51 (3.01-4.09) in males, and 3.45 (2.83-4.22) in females with severe obesity. WTR astigmatism demonstrated the strongest association with BMI, with ORs reaching 2.26 (2.13-2.40) in males and 2.04 (1.90-2.20) in females with severe obesity. The results persisted in a series of subgroup analyses. CONCLUSIONS: Obesity is associated with higher odds of astigmatism in adolescence. Further investigation into the role of weight management in astigmatism development is warranted.

Refractive predictive errors using Barrett II, Hoffer-Q, and SRKT formulae for pediatric IOL implantation.

PURPOSE: To compare the accuracy of the Barrett II universal (BU II) formula, Hoffer-Q, and SRKT formulae following lensectomy and IOL implantation in a large pediatric cohort. METHODS: Retrospective study of children who underwent lensectomy and IOL implantation between 2015 and 2023 at Hadassah-Hebrew University Medical Center, Jerusalem, Israel. RESULTS: One hundred and fifty-one eyes of 104 children aged 6.0 ± 3.9 years were included. The mean prediction error (PE) was - 0.08 ± 1.54 diopters (D) with BU II, 0.24 ± 1.46 D with Hoffer-Q, and 0.71 ± 1.92 D with SRKT (P = 0.10). In eyes with axial length (AL) < 22 mm, BU II and Hoffer-Q had a smaller PE than SRKT (P = 0.024). In eyes with AL ≥ 22 mm, BU II had a smaller PE than Hoffer-Q (P = 0.048). In children 24 months or older at surgery, BU II had a smaller PE than SRKT and Hoffer-Q (P = 0.012). However, in younger children, no difference was found between the formulae (P = 0.61). For mean k-values ≥ 44.5 D, BU II and Hoffer-Q had a smaller PE than SRKT (P = 0.002). An absolute prediction error < 1.0 D was obtained with BU II in 66% of eyes and SRKT in 35% (P = 0.01). CONCLUSIONS: The BU II formula performed well with a small prediction error. No significant difference in PE was detected overall between the formulae. However, only BU II demonstrated a stable prediction error at varying axial lengths, K-readings, and ages. As the biometric parameters of the developing eye change with growth, the BU II formula offers a reliable and stable option for pediatric IOL calculation.

[ARTIFICIAL INTELLIGENCE IN OPHTHALMOLOGY].

INTRODUCTION: Artificial intelligence (AI) was first introduced in 1956, and effectively represents the fourth industrial revolution in human history. Over time, this medium has evolved to be the preferred method of medical imagery interpretation. Today, the implementation of AI in the medical field as a whole, and the ophthalmological field in particular, is diverse and includes diagnose, follow-up and monitoring of the progression of ocular diseases. For example, AI algorithms can identify ectasia, and pre-clinical signs of keratoconus, using images and information computed from various corneal maps. Machine learning (ML) is a specific technique for implementing AI. It is defined as a series of automated methods that identify patterns and templates in data and leverage these to perform predictions on new data. This technology was first applied in the 1980s. Deep learning is an advanced form of ML inspired by and designed to imitate the human brain process, constructed of layers, each responsible for identifying patterns, thereby successfully modeling complex scenarios. The significant advantage of ML in medicine is in its' ability to monitor and follow patients with efficiency at a low cost. Deep learning is utilized to monitor ocular diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, cataract, and retinopathy of prematurity. These conditions, as well as others, require frequent follow-up in order to track changes over time. Though computer technology is important for identifying and grading various ocular diseases, it still necessitates additional clinical validation and does not entirely replace human diagnostic skill.

Driving safety among Israeli military physicians in combat units.

OBJECTIVE: The objective of this study was to characterize driving safety and the factors affecting it among physicians in combat units in the Israel Defense Forces (IDF), who have high workloads and substantial sleep deprivation, which could influence driving safety. METHODS: This cross-sectional study included physicians in combat units who had a personal vehicle equipped with an advanced driver assistance system (ADAS). The study outcomes included events such as drowsy driving or falling asleep while driving, as well as motor vehicle accidents (MVAs), obtained from self-reports from digital questionnaires, and objective ADAS driving safety scores. Sleep hours, burnout scores (Maslach Burnout Inventory), combat activity levels, and demographic characteristics were obtained through digital questionnaires, and their effects on the outcomes were analyzed. RESULTS: Sixty-four military combat unit physicians were included in the study. No differences in drowsy driving, MVAs, or ADAS scores were found between the 2 combat activity level groups. The results showed that 82% of participants reported dozing off while driving, and this was positively correlated with accelerations (ß = 0.19; P = .004) and negatively correlated (adjusted R2 = 21%) with hours of sleep (ß = -0.28; P = .001). Eleven percent reported experiencing MVAs, none of whom required hospitalization. The mean ADAS safety score was 87.17 ± 7.54, and this was positively correlated with the cynicism score (ß = 1.45; P = .04; adjusted R2 = 4.7%). No association between dozing off/falling asleep while driving and the reported MVAs was found (P = .10 and P = .27, respectively). CONCLUSION: Physicians in combat units have a low incidence of MVAs and high ADAS scores. This may be attributed to the high safety climate enforced in military units. However, the high rate of dozing off while driving highlights the importance of addressing driving safety in this population.

Outcome indicators for cross linking in pediatric keratoconus.

Purpose: To evaluate the predictive factors for successful corneal collagen cross-linking (CXL) in pediatric patients with Keratoconus (KC). Methods: This retrospective study was conducted using a prospectively built database. Patients (18 years old or younger) underwent CXL for KC between 2007 and 2017, with a 1-year follow-up period or longer. The outcomes included changes in Kmax (delta [Δ] Kmax = Kmaxlast - Kmaxpre) and LogMAR visual acuity (ΔLogMAR = LogMARlast - LogMARpre).The effects of CXL type (accelerated or non-accelerated), demographics (age, sex, background of ocular allergy, ethnicity), preoperative LogMAR visual acuity, maximal corneal power (Kmax), pachymetry (CCTpre), refractive cylinder, and follow-up (FU) time on the outcomes were analyzed. Results: One hundred thirty-one eyes of 110 children were included (mean age, 16 ± 2 years; range, 10-18 years). Kmax and LogMAR improved from baseline to last visit: from 53.81 D ± 6.39 D to 52.31 D ± 6.06 D (p < 0.001) and from 0.27 ± 0.23 LogMAR units to 0.23 ± 0.19 LogMAR units (p = 0.005), respectively. A negative ΔKmax (meaning corneal flattening) was associated with a long FU, low CCTpre, high Kmaxpre, high LogMARpre, and non-accelerated CXL on univariate analysis. High Kmaxpre and non-accelerated CXL were associated with negative ΔKmax in the multivariate analysis.A negative ΔLogMAR (meaning vision improvement) was associated with a high LogMARpre in univariate analysis. Conclusion: CXL is an effective treatment option in pediatric patients with KC. Our results showed that the non-accelerated treatment was more effective than the accelerated treatment. Corneas with advanced disease had a greater effect on CXL.

The pseudohypopyon stage in adult-onset foveomacular vitelliform dystrophy.

PURPOSE: To gain insight into the pathogenesis of adult-onset foveomacular vitelliform dystrophy (AFVD) via assessment of its pseudohypopyon stage (PHS). METHODS: Retrospectively, data were collected in a tertiary center from established cohorts of a genetically evaluated AFVD and best vitelliform macular dystrophy (BVMD) eyes in the pseudohypopyon stage. Best-corrected visual acuity (BCVA, LogMAR), lesion characterization, including lesion dimensions, liquefaction areas and patterns (altitudinal or lateral), and ellipsoid zone integrity were analyzed from spectral-domain optical coherence tomography images. RESULTS: Out of 167 eyes of 90 AFVD patients and 56 eyes of 28 BVMD patients, 8 eyes of six AFVD patients and five eyes of four BVMD patients were at the PHS were included. The mean LogMAR BCVA ± SD was 0.21 ± 0.20 and 0.41 ± 0.10 in AFVD and BVMD diseases, respectively (p = 0.13). Seven AFVD eyes (87.5%) demonstrated lateral liquefaction, while all BVMD eyes demonstrated an altitudinal pattern (p = 0.005). Maximal horizontal lesion diameters were 1.41 ± 0.46 mm and 2.64 ± 0.77 mm in AFVD and BVMD, respectively (p = 0.02). AFVD patients were older (69 ± 14) than BVMD patients (22 ± 13; p = 0.009). CONCLUSION: The pseudohypopyon stage in AFVD is often characterized by a lateral liquefaction pattern, unlike the altitudinal pattern characterizing BVMD. Age, lesion size, or pathogenesis pathways may underline the different pseudohypopyon stage patterns in AFVD and BVMD.

Central Serous Chorioretinopathy Development following Cessation of Terbinafine Treatment.

This report describes a case of central serous chorioretinopathy (CSCR) occurring following cessation of terbinafine treatment. A 51-year-old man presented for a routine ophthalmic examination. He was treated with oral terbinafine for onychomycosis up to 3 months before the presentation. Spectral-domain optical coherence tomography (OCT) showed extrafoveal subretinal fluid in both eyes with small underlying pigment epithelial detachments. There were no additional relevant findings in the patient history or ocular examination. A diagnosis of CSCR was made. After 10 weeks without treatment, OCT demonstrated almost complete resolution of subretinal fluid in both eyes. The exact key ingredients of the perfect storm leading to CSCR in young, healthy individuals are still unknown. Here, we describe, to our knowledge, the first documented case, where the appearance of CSCR was apparently triggered by cessation of antifungal treatment. This unusual case may provoke further research that will bring us closer to understanding the mechanism behind the appearance of CSCR. It may also widen the scope of the routine anamnesis when dealing with patients newly diagnosed with this enigmatic condition.

Acceptance of Seasonal Influenza Vaccine Following COVID-19 Vaccination: A Survey among Israel Defense Forces Soldiers.

Data regarding the contribution of COVID-19 vaccine rollouts to real-world uptake of influenza vaccination remains unclear. This cross-sectional survey-based study among Israel Defense Forces (IDF) soldiers aimed to assess the impact of the COVID-19 pandemic and specifically, previous COVID-19 vaccines uptake, on the intention to vaccinate for influenza during 2021-2022 season. Participants engaged in an online survey addressing vaccination history and current vaccine-related preferences. The survey was delivered prior to the initiation of the IDF's annual influenza immunization campaign. A multinomial logistic regression model was applied to analyze factors correlated with unwillingness to receive influenza vaccine. Overall, 825 invitations to participate in the survey were distributed and the overall response rate was 78.5%. Among the 648 participants who replied (61.6% males, median age of 20 years), 51.9% were willing to receive the upcoming influenza vaccine. Factors associated with vaccine reluctance included being female, not receiving the previous season's influenza vaccine, not having a previous diagnosis of COVID-19, and having decreased uptake of COVID-19 vaccines. Among participants not intending to receive an influenza vaccine, 50.3% stated that they are healthy and have no need for the vaccine and 36.2% stated they received too many vaccines over the previous year. The results of this study may suggest that influenza vaccination rates in the post-COVID-19 vaccine era may be reduced due to a perceived "vaccine saturation" phenomenon, owing to the density of COVID-19 vaccine administration. Future interventions such as campaigns related to maximizing influenza vaccination coverage should address repeated doses of COVID-19 vaccine administration.

[TREATMENTS FOR PRESBYOPIA].

INTRODUCTION: Presbyopia is the physiological, gradual, progressive loss of the ability to see clearly at near point which affects people as they age. It is primarily caused by the thickening and stiffening of the lens leading to an inability to adjust its shape to become convex enough to induce adequate plus power to see at short distances. Symptoms usually begin affecting individuals around 40 years of age, the most common being discomfort in or around the eyes after prolonged near work, blur at distance after near work, and eventually progressing to near blur, often with a natural tendency to distance the object by holding it farther away to try to see it better. At a certain point near tasks become impossible and the patient will seek an external solution. Various therapies are available and being developed to treat presbyopia, which include glasses, contact lenses, intraocular lens implants, corneal laser procedures, intracorneal implants, scleral alterations and pharmacological ocular drops. Untreated presbyopia negatively affects quality of life as well as the world productivity since presbyopia progresses from approximately an age when people are still an active part of the workforce. As the population and life expectancy grow, so will the number of presbyopes. This article will discuss the various options available to treat presbyopia.

Predicting factors for the efficacy of cross-linking for keratoconus.

PURPOSE: To evaluate predictors for success in corneal crosslinking (CXL) for keratoconus in a large cohort and extended follow-up. DESIGN: A retrospective study based on a prospectively built database. METHODS: Participants underwent CXL for keratoconus from 2007 to 2018. Statistical analysis was performed for patients with at least 1-year follow-up. We analyzed effects of CXL type (Epithelium-on or Epithelium-off and Accelerated (9mW/cm2@10min) or Standard (3mW/cm2@30min)) and pre-operative factors including age, gender, baseline LogMAR visual acuity (LogMARpre), maximal corneal power (Kmaxpre), pachymetry, refractive and topographic cylinders, spherical equivalent (SEpre), mean corneal power (MeanK) and follow-up time on outcome measures. The outcome measures were the final change of Kmax (Delta Kmax) and the final change in LogMAR visual acuity (Delta LogMAR). A more negative Delta Kmax or Delta LogMAR represents a favorable effect of crosslinking. RESULTS: 517 eyes had Kmax results, and 385 eyes had LogMAR results with more than one year follow-up. These eyes were included in the study. The mean follow-up time was 2.29 years. Mean Kmax decreased from 54.07±5.99 diopters to 52.84±5.66 diopters (p<0.001), and Mean LogMAR decreased from 0.28±0.20 to 0.25±0.21 (p<0.001). Non-accelerated epithelium-off CXL resulted in greater flattening of Kmax when compared with other protocols. Visual acuity improvement was similar when comparing different CXL protocols. Multivariate analysis showed four factors associated with negative Delta Kmax: high Kmaxpre, high SEpre, high MeanKpre, and non-accelerated procedure. Multivariate analysis showed three factors associated with negative Delta LogMAR: high LogMARpre, high SEpre, and Low MeanKpre. After excluding corneas with Kmaxpre >65 D or Pachymetry<400 microns, multivariate analysis showed that high Kmaxpre, high SEpre, and non-accelerated CXL were associated with negative Delta Kmax while high LogMARpre and high SEpre were associated with negative Delta LogMAR. CONCLUSION: CXL for keratoconus is a highly effective treatment, as evident by its effects on the outcome measures: Delta Kmax and Delta LogMAR. CXL was more successful in eyes with high Kmaxpre, high SEpre, and high LogMARpre, which express disease severity. The non-accelerated epithelium-off protocol was associated with greater flattening of corneal curvature but did not show a better effect on visual acuity as compared to the other CXL protocols.

Progression of cRORA (Complete RPE and Outer Retinal Atrophy) in Dry Age-Related Macular Degeneration Measured Using SD-OCT.

Purpose: The purpose of this study was to evaluate the long-term rate of progression and baseline predictors of geographic atrophy (GA) using complete retinal pigment epithelium and outer retinal atrophy (cRORA) annotation criteria. Methods: This is a retrospective study. Columns of GA were manually annotated by two graders using a self-developed software on optical coherence tomography (OCT) B-scans and projected onto the infrared images. The primary outcomes were: (1) rate of area progression, (2) rate of square root area progression, and (3) rate of radial progression towards the fovea. The effects of 11 additional baseline predictors on the primary outcomes were analyzed: total area, focality (defined as the number of lesions whose area is >0.05 mm2), circularity, total lesion perimeter, minimum diameter, maximum diameter, minimum distance from the center, sex, age, presence/absence of hypertension, and lens status. Results: GA was annotated in 33 pairs of baseline and follow-up OCT scans from 33 eyes of 18 patients with dry age-related macular degeneration (AMD) followed for at least 6 months. The mean rate of area progression was 1.49 ± 0.86 mm2/year (P < 0.0001 vs. baseline), and the mean rate of square root area progression was 0.33 ± 0.15 mm/year (P < 0.0001 vs. baseline). The mean rate of radial progression toward the fovea was 0.07 ± 0.11 mm/year. A multiple variable linear regression model (adjusted r2 = 0.522) revealed that baseline focality and female sex were significantly correlated with the rate of GA area progression. Conclusions: GA area progression was quantified using OCT as an alternative to conventional measurements performed on fundus autofluorescence images. Baseline focality correlated with GA area progression rate and lesion's minimal distance from the center correlated with GA radial progression rate toward the center. These may be important markers for the assessment of GA activity. Translational Relevance: Advanced method linking specific retinal micro-anatomy to GA area progression analysis.

Outcomes of adalimumab therapy in refractory punctate inner choroidopathy and multifocal choroiditis.

PURPOSE: This study aims to evaluate the outcomes of adalimumab (ADA) therapy in patients with refractory punctate inner choroidopathy (PIC) and multifocal choroiditis (MFC). METHODS: Demographic and clinical data, including LogMAR best-corrected visual acuity (BCVA), were retrospectively collected. Doses of prednisone, immunomodulatory therapies (IMT), and anti-vascular endothelial growth factor (VEGF) injections before and after baseline (ADA initiation) were recorded, as well as the time to clinical remission, time to first flare, and drug-associated adverse events. RESULTS: Seven patients (4 females, ten eyes) were included. The mean follow-up after baseline was 17.8 ± 11.1 months (range 6-33). The mean LogMAR BCVA was 0.35 ± 0.77 at 6 months before baseline and remained stable throughout 12 months after baseline (0.31 ± 0.46 at 12 months; p = 0.47). The mean dose of prednisone decreased from 17.3 ± 19.6 mg/day 6 months before baseline (range 0-60) to 2.6 ± 2.4 mg/day at the last follow-up (range 0-6, p = 0.03). The mean number of flares decreased significantly from 1.43 ± 0.79 over a 6-month period before baseline to 0.2 ± 0.45 (p = 0.02) at 6-12 months after baseline. The mean number of anti-VEGF injections was 4.17 ± 3.92 over the 12-month period before baseline, and it was 2.17 ± 3.06 (p = 0.31) during the first 12 months after baseline. No adalimumab-related adverse events were noted. CONCLUSION: Adalimumab therapy for refractory PIC/MFC enabled a significant steroid-sparing effect, decreased disease flares, and preserved vision over a mean follow-up of 17.8 months.

A column-based deep learning method for the detection and quantification of atrophy associated with AMD in OCT scans.

The objective quantification of retinal atrophy associated with age-related macular degeneration (AMD) is required for clinical diagnosis, follow-up, treatment efficacy evaluation, and clinical research. Spectral Domain Optical Coherence Tomography (OCT) has become an essential imaging technology to evaluate the macula. This paper describes a novel automatic method for the identification and quantification of atrophy associated with AMD in OCT scans and its visualization in the corresponding infrared imaging (IR) image. The method is based on the classification of light scattering patterns in vertical pixel-wide columns (A-scans) in OCT slices (B-scans) in which atrophy appears with a custom column-based convolutional neural network (CNN). The network classifies individual columns with 3D column patches formed by adjacent neighboring columns from the volumetric OCT scan. Subsequent atrophy columns form atrophy segments which are then projected onto the IR image and are used to identify and segment atrophy lesions in the IR image and to measure their areas and distances from the fovea. Experimental results on 106 clinical OCT scans (5,207 slices) in which cRORA atrophy (the end point of advanced dry AMD) was identified in 2,952 atrophy segments and 1,046 atrophy lesions yield a mean F1 score of 0.78 (std 0.06) and an AUC of 0.937, both close to the observer variability. Automated computer-based detection and quantification of atrophy associated with AMD using a column-based CNN classification in OCT scans can be performed at expert level and may be a useful clinical decision support and research tool for the diagnosis, follow-up and treatment of retinal degenerations and dystrophies.

Acquired unilateral visual deterioration: More to ischemia than meets the eye.

A 56-year-old woman presented with visual loss in the right eye with best-corrected visual acuity of 20/40. Funduscopic examination revealed neovascularization of the disk with peripapillary preretinal hemorrhages and leakage on fluorescein angiography. Cerebral arteriography demonstrated stenosis of the major cerebral vessels with classic collaterals configuring as "puff of smoke." A diagnosis of moyamoya-related ocular ischemic syndrome manifesting with optic disk neovascularization was made.

Anti-inflammatory effects of alpha linolenic acid on human corneal epithelial cells.

PURPOSE: Systemic polyunsaturated fatty acids (PUFAs) were shown to improve the symptoms of dry eye syndrome due to their anti-inflammatory effects. This study evaluated the in vitro anti-inflammatory effects of PUFAs on human corneal epithelial (HCE) cells. METHODS: HCE cells were incubated for 2 hours with different concentrations of PUFAs: alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), and linoleic acid (LA). Oleic acid (OA) and dexamethasone (DM) served as negative and positive controls, respectively. Cells were stimulated with either polyinosinic:polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) complex. The protein contents and mRNA expression levels of IL-6, IL-8, IL-1ß, and TNF-α were evaluated with multiplex fluorescent bead immunoassay and real-time PCR, respectively. The expression of inhibitory factor-κBα (I-κBα) was evaluated with real-time PCR. RESULTS: The protein and mRNA levels of IL-6, IL-8, IL-1ß, and TNF-α were significantly increased after stimulation with LPS or poly I:C. Following treatment with ALA, a significant decrease was demonstrated in the protein content of TNF-α to 23.81% (P < 0.001), IL-6 to 46.71% (P < 0.001), IL-1ß to 20.86% (P < 0.05), and IL-8 to 52.21% (P < 0.001). Similar results were demonstrated at the mRNA level. The anti-inflammatory effects of ALA were similar to those of DM for all of the pro-inflammatory cytokines. The ALA inhibition of the pro-inflammatory cytokines was associated with a significant reduction of I-κBα. CONCLUSIONS: ALA may serve as a potent anti-inflammatory agent in ocular surface inflammation. The anti-inflammatory effects of ALA are comparable to those of corticosteroids, and are mediated through NF-κB signal transduction.