Innovative utilization of ultra-wide field fundus images and deep learning algorithms for screening high-risk posterior polar cataract.

PURPOSE: To test a cataract shadow projection theory and validate it by developing a deep learning algorithm that enables automatic and stable posterior polar cataract (PPC) screening using fundus images. SETTING: Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei, Taiwan. DESIGN: Retrospective chart review. METHODS: A deep learning algorithm to automatically detect PPC was developed based on the cataract shadow projection theory. Retrospective data (n = 546) with ultra-wide field fundus images were collected, and various model architectures and fields of view were tested for optimization. RESULTS: The final model achieved 80% overall accuracy, with 88.2% sensitivity and 93.4% specificity in PPC screening on a clinical validation dataset (n = 103). CONCLUSIONS: This study established a significant relationship between PPC and the projected shadow, which may help surgeons to identify potential PPC risks preoperatively and reduce the incidence of posterior capsular rupture during cataract surgery.

Nucleus Near-Infrared (nNIR) Irradiation of Single A549 Cells Induces DNA Damage and Activates EGFR Leading to Mitochondrial Fission.

There has been great interest in identifying the biological substrate for light-cell interaction and their relations to cancer treatment. In this study, a near-infrared (NIR) laser is focused into the nucleus (nNIR) or cytoplasm (cNIR) of a single living cell by a high numerical aperture condenser to dissect the novel role of cell nucleus in mediating NIR effects on mitochondrial dynamics of A549 non-small cell lung cancer cells. Our analysis showed that nNIR, but not cNIR, triggered mitochondrial fission in 10 min. In contrast, the fission/fusion balance of mitochondria directly exposed to cNIR does not change. While the same phenomenon is also triggered by single molecular interactions between epidermal growth factor (EGF) and its receptor EGFR, pharmacological studies with cetuximab, PD153035, and caffeine suggest EGF signaling crosstalk to DNA damaging response to mediate rapid mitochondrial fission as a result of nNIR irradiation. These results suggest that nuclear DNA integrity is a novel biological target for cellular response to NIR.

Two-Step Approach Using Degradable Magnesium to Inhibit Surface Biofilm and Subsequently Kill Planktonic Bacteria.

Bacterial infection remains a great risk in medical implantation surgery. In this paper, we found that degradable metals may be a feasible alternative option of antibacterial implantation materials. It is known that the spalling mechanism of magnesium (Mg) during degradation leads to Mg ions-induced alkaline environment, which is harmful to planktonic bacteria. In this study, we showed that alkaline pH environment is almost harmless to those adhesive bacteria protected in well-formed biofilms. Moreover, experimental results demonstrated that the biofilm formed in the place where Mg spalls are destroyed, releasing the covered bacteria to be planktonic in the alkaline environment. As a result, the colonization of biofilms continues to shrink during the degradation of Mg. It implies that if degradable metal is employed as implantation material, even if bacterial infection occurs, it may be possibly cured without second surgery.

Normalized ocular surface temperature models for tear film characteristics and dry eye disease evaluation.

PURPOSE: To construct normalized ocular surface temperature (NOST) models for different tear film characteristics and evaluate its potential in dry-eyes screening. METHODS: We included 227 right eyes of 227 patients. Tear film characteristics were categorized into 4 types according to fluorescein tear film breakup time (FTBUT) and Schirmer test results, namely type 1: FTBUT >5 s and Schirmer >5 mm; type 2: FTBUT ≤5 s and Schirmer >5 mm; type 3: FTBUT ≤5 s and Schirmer ≤5 mm; and type4: FTBUT >5 s and Schirmer ≤5 mm. Ocular surface temperature was measured by a video-thermographer. Mean temperatures of the central cornea were calculated from the videos of each frame during the 4-s blink interval. We first constructed individual NOST model for every tear characteristic. Participants were included for further analysis when their OSDI was ≥23, FTBUT ≤5 s, and Schirmer >5 mm. They were subdivided into short-BUT and short BUT with SPK subgroups according to the absence or presence of corneal fluorescein-stain. The NOST models of the normal, short-BUT and short BUT with SPK groups were separately constructed and the potential of screening analyzed via ROC curves. RESULTS: Each tear film type had a different NOST model. At 3 s after blinking, the order of NOST was type 4 >type 1 >type 3 >type 2. In dry-eye screening, the NOST was normal > short-BUT > short BUT with SPK. The NOST displayed a sensitivity 0.87, specificity 0.80, and AUC 0.88 for diagnosing short BUT with SPK. CONCLUSION: NOST models are useful in differentiating tear film characteristics and screening dry-eyes. It alleviates the discomfort and inconvenience encountered during conventional dry-eye diagnosis.

Use of Discrete Wavelet Transform to Assess Impedance Fluctuations Obtained from Cellular Micromotion.

Electric cell-substrate impedance sensing (ECIS) is an attractive method for monitoring cell behaviors in tissue culture in real time. The time series impedance fluctuations of the cell-covered electrodes measured by ECIS are the phenomena accompanying cellular micromotion as cells continually rearrange their cell-cell and cell-substrate adhesion sites. Accurate assessment of these fluctuations to extract useful information from raw data is important for both scientific and practical purposes. In this study, we apply discrete wavelet transform (DWT) to analyze the concentration-dependent effect of cytochalasin B on human umbilical vein endothelial cells (HUVECs). The sampling rate of the impedance time series is 1 Hz and each data set consists of 2048 points. Our results demonstrate that, in the Daubechies (db) wavelet family, db1 is the optimal mother wavelet function for DWT-based analysis to assess the effect of cytochalasin B on HUVEC micromotion. By calculating the energy, standard deviation, variance, and signal magnitude area of DWT detail coefficients at level 1, we are able to significantly distinguish cytotoxic concentrations of cytochalasin B as low as 0.1 µM, and in a concentration-dependent manner. Furthermore, DWT-based analysis indicates the possibility to decrease the sampling rate of the micromotion measurement from 1 Hz to 1/16 Hz without decreasing the discerning power. The statistical measures of DWT detail coefficients are effective methods for determining both the sampling rate and the number of individual samples for ECIS-based micromotion assays.

Selective Regulation of Neurons, Glial Cells, and Neural Stem/Precursor Cells by Poly(allylguanidine)-Coated Surfaces.

Poly(allylguanidine) (PAG) was synthesized and characterized as a polycationic coating material for culturing neurons, glial cells, and neural stem/precursor cells (NSPCs) to apply PAG for neural tissue engineering. For comparison, poly-d-lysine (PDL), the golden benchmark of the neuron cell culture system, was also used in this study. When PAG was subjected to a mixed culture of neurons and glial cells, cell adhesion and neurite extension of neuronal cells were clearly observed but only few glial cells could be found alongside the neurons. Compared to PDL, the significantly lower density of the glial fibrillary acidic protein-positive cells implied that PAG suppressed the glial cell development. Likewise, PAG was demonstrated to dominate the differentiation of NSPCs principally into neurons. To investigate whether the different effects of PAG and PDL on neuron and glial cell behaviors resulted from the difference of guanidinium cations and ammonium cations, poly-l-arginine (PLA) was included and compared in this study. Similar to PDL, PLA supported high neuron and glial cell viability simultaneously. Consequently, glial cell growth and viability restrained on PAG was not only affected by the side-chain guanidino groups but also by the backbone structure property. The absence of the peptide structure in the backbone of PAG and the conformation of coated PAG on tissue culture polystyrene possibly determined the polycationic biomaterial to limit the growth of glial cells.

Infrared thermography in the evaluation of meibomian gland dysfunction.

BACKGROUND/PURPOSE: To evaluate meibomian gland dysfunction (MGD) by infrared thermography. METHODS: An observational study was conducted at the Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan. Participants included 89 MGD patients (30 in Grade 1, 49 in Grade 2, and 10 in Grade 3) and 65 controls. The close-eye thermographic images of the eyelid were obtained noninvasively by infrared thermography. Temperatures at 8 regions of interest (ROIs) of the eyelid margin and a reference temperature at the center of the upper eyelid were measured. The temperature ratio was defined as the temperature of ROI divided by the reference temperature. RESULTS: Eyelid margin temperature measured by infrared thermography increased from temporal side (ROI 1) to the nasal side (ROI 8) of the eye in both MGD patients and control groups. The temperature ratios were significantly higher in MGD participants than in controls, especially at ROI 8. CONCLUSION: The eyelid margin temperature measured by infrared thermography was higher in MGD participants. Further development of this infrared thermography system may become a rapid and non-invasive tool for MGD screening.

Influence of ocular features and incision width on surgically induced astigmatism after cataract surgery.

PURPOSE: To identify factors associated with surgically induced astigmatism (SIA) following phacoemulsification. METHODS: Six hundred five eyes underwent phacoemulsification with a 2.2-mm (the 2.2-mm group, n = 248) or 2.75-mm (the 2.75-mm group, n = 357) superior limbal incision. Preoperative axial length, anterior chamber depth, corneal curvature, and intra-ocular pressure were measured. Corneal curvature and intraocular pressure were measured at 1 day, 1 week, and 1, 2, and 3 months postoperatively. SIA, corneal flattening, and torque were calculated using the Alpins method. The effect of preoperative corneal astigmatism meridian on SIA was also examined. Differences in SIA between the 2.2- and 2.75-mm groups were explored, and correlations between SIA and preoperative corneal astigmatism, anterior chamber depth, axial length, age, and intraocular pressure were analyzed. RESULTS: SIA, corneal flattening, and torque were smaller in the 2.2-mm group than in the 2.75-mm group at 1 week (P = .003, .006, and .014, respectively), but not statistically different thereafter. Higher preoperative corneal astigmatism, older age, and shallower anterior chamber depth were associated with greater SIA in both groups. The effect of astigmatism meridian on SIA was more noticeable in the 2.75-mm group. Shorter axial length and lower intraocular pressures were associated with greater SIA in the 2.75-mm group but not in the 2.2-mm group. CONCLUSIONS: Reducing limbal incision width and considering patient age, the meridian and magnitude of corneal astigmatism, anterior chamber depth, axial length, and intraocular pressure, and adjusting the flattening component of SIA input for toric intraocular lens power calculation could potentially improve the astigmatism control in refractive lens surgery.

Correlations among ocular surface temperature difference value, the tear meniscus height, Schirmer's test and fluorescein tear film break up time.

PURPOSE: To report the use of a thermographer for measuring ocular surface temperature, and to evaluate the correlation among the obtained temperature difference values (TDVs) and dry eye parameters (tear meniscus height (TMH); Schirmer's test results; fluorescent tear breakup time (FTBUT)). METHODS: Forty-three participants (age 40.2±14.7 years; range 21-67 years) from Far Eastern Memorial Hospital, Taiwan were recruited for the study. The surface temperature was measured at the centre of the ocular surface for 4 s after blinking. TDV was defined as the change in corneal surface temperature relative to that of the preceding eye opening, where TDV01, TDV02, TDV03, and TDV04 represent the values obtained 1, 2, 3, and 4 s after blinking, respectively. Anterior segment optical coherence tomography (AS-OCT) was employed to measure the lower TMH. Schirmer's test with topical anaesthetic was conducted to measure the basal tear secretion. The FTBUT was recorded using a digital camera. RESULTS: TDV measurement exhibited high reliability (intraclass correlation coefficient=0.91). TDV03 exhibited the highest significance and strongest positive correlation with the TMH (r=0.52, p=0.0003) and Schirmer's test value (r=0.39, p=0.008), whereas the TDV03-FTBUT correlation was non-significant. Age correlated negatively and significantly with the TDV (r= -0.35, p=0.021), TMH (r= -0.33, p=0.031), and Schirmer's test value (r= -0.31, p=0.044). TDV03 remained significantly correlated with the TMH and Schirmer's test value after adjustment for age. CONCLUSIONS: The thermographer was effective in capturing temperature changes in the ocular surface. The temperature difference 3 s after blinking appears to be correlated with lower TMH and Schirmer test values.

Direct observation and validation of fluorescein tear film break-up patterns by using a dual thermal-fluorescent imaging system.

The fluorescein tear film break-up test is a common tear film stability test for dry eye diagnosis. This test requires applying fluorescein sodium drops to a tear film to observe the tear film break-up. However, this test is limited by using the fluorescein sodium drops, which can induce reflex tearing and reduce the reliability of the diagnosis results. This paper proposes that tear film evaporation accelerates on the fluorescein tear film break-up area (FTBA), resulting in a lower temperature area (LTA) on the tear film. A dual modality system was established to capture the thermal and fluorescent image of fluorescein-stain tear films for 48 participants. Observations showed that the LTA and FTBA were highly correlated in their location (r = 0.82) and size (r = 0.91). This is first study to show that the FTBA and LTA are essentially the same region. This study demonstrated the feasibility of using the noncontact thermograph method to evaluate tear film stability without using a fluorescein sodium drop.

Noncontact detection of dry eye using a custom designed infrared thermal image system.

Dry eye syndrome is a common irritating eye disease. Current clinical diagnostic methods are invasive and uncomfortable for patients. This study developed a custom designed noncontact infrared (IR) thermal image system to measure the spatial and temporal variation of the ocular surface temperature over a 6-second eye-open period. This research defined two parameters: the temperature difference value and the compactness value to represent the temperature change and the irregularity of the temperature distribution on the tear film. Using these two parameters, this study achieved discrimination results for the dry eye and the normal eye groups; the sensitivity is 0.84, the specificity is 0.83, and the receiver operating characteristic area is 0.87. The results suggest that the custom designed IR thermal image system may be used as an effective tool for noncontact detection of dry eye.