Schirmer test results are widely used for ocular surface disease assessment, but Schirmer strips are not standardized. We compare the characteristics and tear volume with millimeter moisture ...migration in different brands of Schirmer strips and introduce methods for volume-based, brand-independent calibration.
Physical parameters of Haag-Streit, EagleVision, TearFlo, Contacare, and MIPL/A6 Schirmer strip brands were compared. Schirmer strip millimeter moisture migration distances were assessed 5 minutes after application of incremental microliter volumes of human tears. Linear regression analysis of data points from each Schirmer strip brand was performed, and the root-mean-square deviation of data points to the best-fit linear regression was calculated. Calibration correction was performed by converting migration distance to the corresponding tear volume. A reference table and calibration method formulas were created.
Schirmer strips differed in design, shape, and manufacturing precision. Strip width, weight, and length were different between the 5 brands ( P < 0.05). A wide range of Schirmer strip moisture migration values for identical tear volumes was observed among brands. Statistical measurement resulted in a root-mean-square deviation of 2.9 mm for all data points from all brands. Millimeter to volume and weight to volume-based calibration correction methods resulted in a 2.2- and 3.1-fold measurement error reduction, respectively.
Our findings highlight the lack of standardization among different brands of Schirmer strips, raising concerns about potential sources of unintentional measurement errors. We propose volume-based Schirmer strip calibration methods and conversion of millimeter to microliter results to achieve brand-independent results and improve Schirmer test accuracy.
γ-Crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to ...prevent scattering of light and formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens γ-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including nonlens members of the βγ-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens and thereby reduce their propensity to aggregate and form cataracts. To produce a significant increase in the refractive index increment, a substantial global shift in amino acid composition is required, which can naturally explain the highly unusual amino acid composition of γ-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure.
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► Lens γ-crystallins have evolved to an unusually high molecular refractive index, dn/dc. ► In parallel evolution, cephalopod S-crystallins have evolved the same trait. ► A high dn/dc requires a global shift towards unusual amino acid compositions. ► Macromolecular crowding in high-density lenses is the thermodynamic driving force. ► The γ-crystallin structure serves as a stable scaffold for accommodating replacements.
Abstract
Objective
Reticular pseudodrusen (RPD), a key feature of age-related macular degeneration (AMD), are poorly detected by human experts on standard color fundus photography (CFP) and typically ...require advanced imaging modalities such as fundus autofluorescence (FAF). The objective was to develop and evaluate the performance of a novel multimodal, multitask, multiattention (M3) deep learning framework on RPD detection.
Materials and Methods
A deep learning framework (M3) was developed to detect RPD presence accurately using CFP alone, FAF alone, or both, employing >8000 CFP-FAF image pairs obtained prospectively (Age-Related Eye Disease Study 2). The M3 framework includes multimodal (detection from single or multiple image modalities), multitask (training different tasks simultaneously to improve generalizability), and multiattention (improving ensembled feature representation) operation. Performance on RPD detection was compared with state-of-the-art deep learning models and 13 ophthalmologists; performance on detection of 2 other AMD features (geographic atrophy and pigmentary abnormalities) was also evaluated.
Results
For RPD detection, M3 achieved an area under the receiver-operating characteristic curve (AUROC) of 0.832, 0.931, and 0.933 for CFP alone, FAF alone, and both, respectively. M3 performance on CFP was very substantially superior to human retinal specialists (median F1 score = 0.644 vs 0.350). External validation (the Rotterdam Study) demonstrated high accuracy on CFP alone (AUROC, 0.965). The M3 framework also accurately detected geographic atrophy and pigmentary abnormalities (AUROC, 0.909 and 0.912, respectively), demonstrating its generalizability.
Conclusions
This study demonstrates the successful development, robust evaluation, and external validation of a novel deep learning framework that enables accessible, accurate, and automated AMD diagnosis and prognosis.
Abstract
Background
Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory ...response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative cerebrospinal fluid (CSF) cultures. Data on effective treatment are limited.
Methods
Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky performance scores, magnetic resonance imaging (MRI) brain scanning, ophthalmic and audiologic exams, and CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion.
Results
The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (P < .0003), which was accompanied by improvements in CSF glucose, white blood cell (WBC) count, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (P < .003). All patients with papilledema and visual field deficits also exhibited improvement (P < .0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (P = .001). CSF cultures remained negative.
Conclusions
PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.
This is a small case series describing functional outcomes in previously healthy cryptococcal meningitis patients treated with pulse corticosteroid taper therapy for postinfectious inflammatory syndrome (PIIRS).
The purpose of this study was to investigate the long-term visual dysfunction in patients after blast-induced mild traumatic brain injury (mbTBI) using a retrospective case series of 31 patients with ...mbTBI (>12 mo prior) without eye injuries. Time since mbTBI was 50.5 +/- 19.8 mo. Age at the time of injury was 30.0 +/- 8.3 yr. Mean corrected visual acuity was 20/20. Of the patients, 71% (n = 22) experienced loss of consciousness; 68% (n = 15) of patients in this subgroup were dismounted during the blast injury. Overall, 68% (n = 21) of patients had visual complaints. The most common complaints were photophobia (55%) and difficulty with reading (32%). Of all patients, 25% were diagnosed with convergence insufficiency and 23% had accommodative insufficiency. Patients with more than one mbTBI had a higher rate of visual complaints (87.5%). Asymptomatic patients had a significantly longer time (62.5 +/- 6.2 mo) since the mbTBI than symptomatic patients (42.0 +/- 16.4 mo, p < 0.004). Long-term visual dysfunction after mbTBI is common even years after injury despite excellent distance visual acuity and is more frequent if more than one incidence of mbTBI occurred. We recommend obtaining a careful medical history, evaluation of symptoms, and binocular vision assessment during routine eye examinations in this prepresbyopic patient population.
To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs.
DeepLensNet was trained by applying deep ...learning models to the Age-Related Eye Disease Study (AREDS) dataset.
A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants).
Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students.
Mean squared error (MSE).
On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation SD, 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC.
DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.
Abstract
Introduction
To evaluate the long-term refractive results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) performed by the military in a veteran population.
...Materials and Methods
Three Department of Veterans Affairs (VA) hospital sites (Puget Sound, Buffalo, and Washington D.C.) obtained IRB approval for this multi-center study. Comprehensive ophthalmologic assessment including refraction and keratometry were obtained at the time of the long-term VA examination and compared to the patients’ postoperative military records.
Results
Eighty patients (160 eyes) enrolled in this study. At the time of treatment, patients were 21–52 years of age. Long-term post-operative data was available from 4 to 17 years post-operatively. Fifteen percent of the treatment types were LASIK and 85% PRK. At the time of their military post-operative exam (range 3–14 months, mean 4 months), 82% of patients had uncorrected visual acuity (UCVA) of 20/20 or better, and their average manifest refraction was −0.08 D (SD ± 0.48 D). At the time of the long-term ophthalmological exam at the VA medical centers (range 4–11 years, mean of 8.2 years), 49% of patients had an UCVA of 20/20 or better and an average manifest refraction was −0.64 D (SD ± 0.69 D).
Conclusion
This is the first long-term study evaluating refractive surgery outcomes up to 17 years in a military population. Our study demonstrates safety after refractive surgery in the military with less than 0.1D increase in myopia per year and strong keratometric stability. Other changes in the eye may be the likely cause for this observed mild refractive shift.
To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies.
...Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy.
Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs.
We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.
Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) ...enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.
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