Search

The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs.

Peripapillary and macular vessel density (VD) are reduced in myopic non-glaucomatous eyes, the dynamic range of VD may be decreased by myopia, and whether VD measurement has the potential in differentiating stages of glaucoma severity in patients with myopic glaucoma remains questionable. This observational, cross-sectional study aimed to clarify the changes in peripapillary and macular VDs in preperimetric glaucoma (PPG) and primary open-angle glaucoma in the early, moderate, and late stages. A total of 1228 eyes from 661 participants (540 normal, 67 PPG, and 521 glaucomatous) were included. Participants underwent free blood tests at the internal medicine clinic to retrieve systemic data. Patients with glaucoma were grouped by disease severity, defined by glaucomatous visual field mean defect, including early-(224 eyes), moderate-(103 eyes), and late-stage glaucoma (194 eyes), and further divided into advanced (158 eyes) and terminal glaucoma (36 eyes). Macular VD, peripapillary VD, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and ganglion cell complex (GCC) thickness were evaluated and divided into superior and inferior parts. One-way analysis of variance was performed, followed by Tukey’s post-hoc test. The peripapillary VD was significantly different between the healthy and PPG groups and the early-, moderate-, and late-stage glaucoma subgroups (all p < 0.001). Peripapillary VD measurements are helpful in differentiating the various stages of glaucoma even in patients with myopic glaucoma.

Background/Purpose: To investigate the knowledge and learning ability of glaucoma patients regarding their anti-glaucoma topical medications. Methods: Patients on regular follow-up at the Glaucoma Clinic at Hsin-Chu General Hospital were recruited. After detailed ocular examinations, the participants were asked to recall and identify their glaucoma eye drops. The same test was repeated 3 months later. The results of both tests, the learning ability of patients regarding their glaucoma drugs, and the relationship between learning ability and demographic variables were evaluated. Results: Two hundred eighty-seven glaucoma patients participated in this study. Of the study population, 25.8% and 57.1% could recall their topical mediation at the first and second tests, whereas 72.1% and 88.5% could identify their prescribed eye drops at the first and second tests, respectively. Approximately 34% of the participants showed improved knowledge at the repeat test, whereas 40% of the participants showed no improvement. Participants with a better learning ability were more likely to be younger, with a higher level of education, and with less visual field impairment. Conclusion: The knowledge of glaucoma patients regarding their prescribed medication was deficient in Taiwan. Physician effort could improve knowledge on the prescribed drugs. Patient-centered education should be considered, targeting elderly individuals, illiterate individuals, and those with loss of visual function to increase compliance with glaucoma medication. Keywords: Glaucoma drugs, Identification, Knowledge, Recalling

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-&beta, ) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-&beta, in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-&beta, related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-&beta, 1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-&beta, enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-&beta, mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1&alpha, ). Summarizing, our results demonstrated that TGF-&beta, keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.

Glaucoma is the second leading causes of vision loss in the world after cataract and irreversible, particularly among the elderly, several years past, most of the molecular mechanisms leading to primary open angle glaucoma (POAG) are still unknown, however scientists discovered ascorbic acid (AA) concentration is reduced in cataract and glaucomatous patients aqueous humor compared with healthy eyes.For understand relationship between AA concentration and glaucoma, we try to develop a simple, sensitive and accurate sensor device for detection in AA . Electrochemical sensor featured with short analytical time, low cost, high sensitivity compared with other methods, in this work, a new electrochemical aptamer sensor for detecting AA was fabricated based on AA specific aptamer linked with polydopmine (PD) layer and immobilized on screen printed carbon electrode (SPCE). Cyclic voltammetry (CV) was used to investigate AA concentration dropped on modified electrode .Both analyze real human aqueous humor sample or commercial AA solution , aptamer electrode performed a good accuracy compared with high performance liquid chromatography (HPLC).

The retinal nerve fibre layer (RNFL) thickness is reportedly decreased in myopia; however, magnification adjustment is an important consideration when using optical coherence tomography (OCT) to evaluate myopic eyes. In this study, RNFL thickness and optic nerve head (ONH) size were measured in highly myopic eyes with and without magnification adjustments. The measurements were compared with magnification-adjusted OCT measurements of emmetropic control eyes.In this cross-sectional study, RNFL thickness (global circle and quadrants) and ONH size (disc and rim areas) were measured in one eye of each of 70 participants with high myopia. Magnification-adjusted measurements taken in the high myopes were then compared with magnification-adjusted measurements taken in 70 emmetropic controls.Comparisons of magnification-adjusted measurements between highly myopic and emmetropic control eyes showed that the highly myopic eyes had significantly thicker global and temporal RNFLs (p0.05), significantly thinner nasal RNFL (p0.05), and significantly larger disc and rim areas (p0.05). Superior and inferior RNFL thickness measurements did not differ significantly between the two groups (p0.05).The OCT measurements obtained with magnification adjustment show global and temporal RNFL thicknesses and ONH size increase in highly myopic eyes.

Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia–reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

Purpose This study investigates the influence of age and axial length (AL) on the peripapillary retinal nerve fiber layer (RNFL) thickness, as measured by optical coherence tomography (OCT). Methods Healthy patients visiting an eye clinic at a county hospital were recruited. All participants underwent comprehensive ophthalmologic examinations, and their retinas were scanned using 3D OCT-1000. In total, 223 patients with 446 eyes were included. The mean age and AL were 42.07 ± 13.16 (21–76) years and 25.38 ± 1.73 (21.19–30.37) mm, respectively. Results The average RNFL thickness decreased by 2.71 μm for every 10-year increase in age (P < 0.001). Age-related RNFL thinning was more significant in participants older than 41 years (-0.24μm/year; P = 0.015). The earliest sector showing a significant decline in RNFL thickness was after 35 years of age (-0.70μm/year; P = 0.011) at the superior quadrant and at the 1–2 o’clock hour (-1.42μm/year; P = 0.009). Meanwhile, the maximal rate of age-associated RNFL decay was observed in these two regions as well. The reduction of RNFL with age progression did not differ in eyes with long AL (> 27 mm; -0.16μm/year) or those with short AL (< 25 mm; -0.22μm/year). For every 1-mm-greater AL, RNFL was thinner by 1.78 μm (P < 0.001). The inferior quadrant showed the greatest tendency of RNFL decline with longer AL (4.46 μm/mm; P < 0.001). Conclusions The factors of age and AL should be considered when interpreting the results. Significantly age-associated RNFL thinning was found in participants older than 41 years. Reduction of RNFL thickness with increasing age was not affected by AL. Topographic variations in RNFL thinning were observed in that the maximal decline of RNFL thickness with advancing age at the superior quadrant whereas with elongation of AL at the inferior quadrant.

The pupil response to light can reflect various kinds of neural diseases, and different response for two eyes can be analyzed relative afferent pupillary defect. This study presents the novel wearable pupillometer for recording the pupil response and designs the experiment for verifying the synchronization of two cameras. Compared with other devices, the main feature of this study is proven reliable, portable, and wearable for obtaining the pupil response. In addition, our experimental result verify that the pupillometer successfully achieve the function of synchronization.

The pupil response to light can reflect various kinds of diseases which are related to physiological health. Pupillary abnormalities may be influenced on people by autonomic neuropathy, glaucoma, diabetes, genetic diseases, and high myopia. In the early stage of neuropathy, it is often asymptomatic and difficulty detectable by ophthalmologists. In addition, the position of injured nerve can lead to unsynchronized pupil response for human eyes. In our study, we design the pupilometer to measure the binocular pupil response simultaneously. It uses the different wavelength of LEDs such as white, red, green and blue light to stimulate the pupil and record the process. Therefore, the pupilometer mainly contains two systems. One is the image acquisition system, it use the two cameras modules with the same external triggered signal to capture the images of the pupil simultaneously. The other one is the illumination system. It use the boost converter ICs and LED driver ICs to supply the constant current for LED to maintain the consistent luminance in each experiments for reduced experimental error. Furthermore, the four infrared LEDs are arranged nearby the stimulating LEDs to illuminate eyes and increase contrast of image for image processing. In our design, we success to implement the function of synchronized image acquisition with the sample speed in 30 fps and the stable illumination system for precise measurement of experiment.

Background The aim here was to investigate whether optic nerve head (ONH) parameters or retinal nerve fibre layer (RNFL) thickness correlate with age or disc area and whether the neuroretinal rim correlates with RNFL thickness. Methods This cross-sectional study enrolled 133 healthy subjects and analysed one randomly selected eye of each subject. All measurements of ONH parameters (including neuroretinal rim, disc and cup areas and cup-to-disc ratios) and RNFL thickness (global and quadrants) were taken by a single experienced operator using optical coherence tomography (OCT). Results Of the rim parameters analysed, average nerve width (the height of the nerve fibre bundle) was independent of age or disc area (p > 0.05). Disc area correlated positively with cup area (p 0.05). Of the RNFL thickness measurements analysed, temporal RNFL was independent of both age and disc area (p > 0.05). According to the analysis of the correlation between RNFL thickness and neuroretinal rim, global or non-temporal RNFL correlated positively with horizontal integrated rim width (p 4.000) and temporal RNFL was independent of all rim parameters (p > 0.05, F < 4.000). Conclusion Aging effect on neuroretinal rim loss or RNFL thickness change is non-uniform, and age is not a constant confounder when using OCT. The temporal RNFL is independent of age, disc area and neuroretinal rim.

We investigated the balance of free radicals in retinas at various time points after chronically elevating intraocular pressures in rats. The left eyes of female Wistar rats were divided into five intraocular pressure elevation (IOPE) subgroups after cauterization of three episcleral veins (1 day, 3 days, 1 week, 3 weeks, and 5 weeks) and time-related sham controls. Chemiluminescence levels were examined in isolated retinas. The nitroblue tetrazolium (NBT) incubation method was also performed to confirm the superoxide expression. The activities of antioxidant enzymes and lipid peroxides in isolated retinas were detected by spectrophotometry. In the IOPE group, the intraocular pressure after cauterization was around 22-30 mm Hg; chemiluminescence levels of isolated retinas were significantly elevated on day 3 and week 1; there were more NBT-positive retinal ganglion cells on day 1 and day 3; lipid peroxidation also increased significantly from day 1 and came back to the baseline on week 5; the activities of superoxide dismutases and catalase rose on week 1. Intraocular pressure elevation was shown to change the free radical balance. We suggest that free radicals and their oxidative stresses may play a role in the early stage of glaucoma in causing retinal ganglion cell death in our rat model.

The intraocular pressure (IOP) that can diagnose or track glaucoma generally because it is one of the physiology parameters that are associated with glaucoma. But IOP is not easy and consistence to be measured under different measure conditions. Besides, diabetes is associated with diabetic autonomic neuropathy (DAN). Pupil size response might provide an indirect means about neuronal pathways, so the abnormal pupil size may relate with DAN. Hence an infrared videopupillography is needed for tracking glaucoma and exploring the relation between pupil size and DAN. Our previous research proposed an infrared videopupillography to monitoring the pupil size of different light stimulus in dark room. And this portable infrared videopupillography contains a camera, a beam splitter, the visible-light LEDs for stimulating the eyes, and the infrared LEDs for lighting the eyes. It can be mounted on any eyeglass frame. But it can modulate only two dimensions, we cannot zoom in/out the eyes. Moreover, the eye diameter curves were not smooth and jagged because of the light spots, lone eyelashes, and blink. Therefore, we redesign the optical path of our device to have three dimension modulation. Then we can zoom in the eye to increase the eye resolution and to avoid the LED light spots. The light spot could be solved by defining the distance between IR LED and CCD. This device smaller volume and less prices of our previous videopupillography. We hope this new infrared videopupillography proposed in this paper can achieving early detection about autonomic neuropathy in the future.

We investigated the effect of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival after intraocular pressure (IOP) elevation at various time intervals. In adult Wistar rats, RGCs were labeled with 5% Fluorogold. Animals with 1.8-2.5-fold increase in IOP after cauterization of three episcleral vessels, were divided into three BDNF groups and three vehicle control groups, each receiving one, two or three injections. The RGC survival percentage on RGCs of the first, second and third injections were 93.9% (n = 7), 91.3% (n = 7), 82.7% (n = 5), respectively in BDNF groups; 91.6% (n = 6), 84.1% (n = 6) and 73.5% (n = 5), respectively in vehicle controls. The second and third injections of BDNF showed statistically significant survival effects. These findings demonstrated that BDNF has partial neuroprotection on RGCs in whole retina and enhances RGC survival in moderately chronic hypertensive eyes.

Glaucoma was diagnosed or tracked by the intraocular pressure (IOP) generally because it is one of the physiology parameters that are associated with glaucoma. But measurement of IOP is not easy and consistence under different measure conditions. An infrared videopupillography is apparatus to monitor the pupil size in an attempt to bypass the direct IOP measurement. This paper propose an infrared videopupillography to monitoring the pupil size of different light stimulus in dark room. The portable infrared videopupillography contains a camera, a beam splitter, the visible-light LEDs for stimulating the eyes, and the infrared LEDs for lighting the eyes. It is lighter and smaller than the present product. It can modulate for different locations of different eyes, and can be mounted on any eyeglass frame. An analysis program of pupil size can evaluate the pupil diameter by image correlation. In our experiments, the eye diameter curves were not smooth and jagged. It caused by the light spots, lone eyelashes, and blink. In the future, we will improve the analysis program of pupil size and seek the approach to solve the LED light spots. And we hope this infrared videopupillography proposed in this paper can be a measuring platform to explore the relations between the different diseases and pupil response.

Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. The purpose of this study was to investigate the effect of simvastatin on retinal neurons and the expression of apoptotic proteins in a rat IR model. Wistar rats received intravitreal injection of simvastatin immediately after retinal reperfusion. Retinal ischemia was induced by increasing intraocular pressure to 150 mm Hg for 60 min. The number of viable RGCs was measured after retrograde labeling with Fluoro-Gold. Ischemia-induced apoptotic cell death was studied using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). We found that simvastatin treatment enhanced RGC survival after retinal ischemia by approximately 40% and decreased retinal neuronal apoptosis. Using western blot analysis, we found that simvastatin upregulated the expression of Bcl-2 in the retina. In contrast, the level of the protein Bax was unaffected by simvastatin treatment. Our results suggest that RGC loss induced by retinal IR may be prevented by simvastatin and that the mechanism underlying this process possibly involves an alteration in the apoptotic pathway.

Investigate the effect of dietary vitamin E (Vit E) on the retinas of a rat model of induced glaucoma, in which surgically induced elevation of intraocular pressure (IOP) is associated with an increase in reactive oxygen species.Rats were fed a standard chow, Vit E-supplemented diet, or Vit E-deficient diet and subjected to surgically induced IOP elevation (or sham surgery) for five weeks. The retinal ganglion cells (RGCs) were subjected to retrograde fluorescent tracer labeling.The mean number of RGCs of rats on the standard chow, Vit E-supplemented diet, and Vit E-deficient diet were 79.6%, 78.6%, and 71.3% of controls, respectively. Lipid peroxidation of the retinas of rats given a Vit E-deficient diet were significantly higher after IOP elevation for three days (14.42 +/- 0.25 microM, P = 0.016) and five weeks (10.46 +/- 0.11 microM, p = 0.042), compared to rats given standard chow (11.37 +/- 0.31 microM; 8.95 +/- 0.16 microM). Compared with rats given standard chow, rats given a Vit E-deficient diet had significantly elevated concentrations of glutathione (p = 0.032), but no significant differences in the levels of total superoxide dismutase (SOD), Cu/Zn SOD, or catalase activities three days after IOP elevation.Rats fed a Vit E-deficient diet with surgically induced IOP elevation experience significantly more RGC death than rats fed a normal diet. This phenomenon may be related to the increased level of lipid peroxidation in Vit E-deficient rats.

RGC (retinal ganglion cell) death following ischaemic insult is the major cause of a number of vision-threatening diseases, including glaucoma. The aim of the present study was to evaluate the role of HO-1 (haem oxygenase-1) in the retina against IR (ischaemia/reperfusion) injury. Adenovirus-mediated HO-1 gene transfer (Adv-HO-1) was carried out by injection into the vitreous body to induce HO-1 overexpression. At 3 weeks after transfection, levels of HO-1 expression, as measured by Western blot analysis, immunohistochemical staining and activity assay, were drastically up-regulated. Transient retinal ischaemia was induced by raising the intraocular pressure to 150 mmHg for 60 min. Untreated IR caused a significant decrease in RGC numbers at 3 and 7 days after reperfusion (76.1 and 67.2% of control eyes with sham IR respectively; P

Retinal ischemia/reperfusion (IR) injury causes profound tissue damage, especially retinal ganglion cell death. The aims of the study were twofold: (1) to investigate the benefits of epigallocatechin-3-gallate (EGCG), the major catechin found in tea, after IR challenge, and (2) to elucidate the mechanism of EGCG inhibition of nitric oxide synthase (NOS) expression. Wistar female rats were divided into four groups: normal control, EGCG with sham operation, retinal IR, and EGCG with IR groups. EGCG (50 mg/kg) was administered by intraperitoneal injection 30 min before the experiment. IR injury to a rat's retina was induced by raising intraocular pressure to 150 mmHg for 60 min. With EGCG pretreatment, retinal ganglion cell death from IR was reduced by approximately 10% 3 days afterward. EGCG significantly downregulated IR-induced glial fibrillary acidic protein expression. EGCG treatment also reduced TUNEL-positive cells after IR in the inner retina as well as IR-induced lipid peroxidation. Histological analyses showed fewer neuronal NOS and nicotinamide adenine dinucleotide phosphate diaphorase-positive cells in the retina after IR with EGCG administration. Therefore, EGCG is effective in protecting retinal ganglion cells from IR challenge by ameliorating retinal nitrosactive stress and by regulating cell death through apoptotic pathways.