Comparison of clinical usefulness of central 30-2 and 24-2 threshold tests using SITA strategy.

PURPOSE: To compare the clinical utilities of the SITA-based central 24-2 and 30-2 threshold tests. METHODS: Three hundred sixty-five (365) eyes of 183 glaucoma and glaucoma suspect patients who had undergone both central 30-2 and 24-2 threshold testing using the Swedish interactive threshold algorithm (SITA) standard strategy were retrospectively reviewed. The tests were performed in patients with a minimum visual acuity of LogMAR best-corrected visual acuity (BCVA) 0.3. We compared test time, fixation loss (%), false-positive error rate (%), and false-negative error rate (%), all of which are indices of reliability. We additionally compared the mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI), all of which are indices of the visual field test. RESULTS: The mean age was 54.67 ± 14.95. MD, VFI, and fixation loss showed no significant difference between the 30-2 and 24-2 tests. As expected, 24-2 was shorter in duration: 5.64 ± 1.09 min versus 7.51 ± 1.38 min (p < .001), a 24.51 ± 9.45% difference. The false-positive error rate was significantly higher, but the false-negative error rate was lower, with the 24-2 threshold test (p = .009, p < .001). The PSD also was lower with 24-2 than with 30-2 (p < .001). CONCLUSION: The two tests' VFI and MD are comparable. The 24-2 test may be a more efficient examination for most patients in terms of test time. In the other relevant aspects, the two tests are not identical. Therefore, it would be advisable to tailor visual field testing to the individual patient.

Digital Therapeutics: Exploring the Possibilities of Digital Intervention for Myopia.

Pediatric myopia is increasing globally and has become a major public health issue. However, the mechanism of pediatric myopia is still poorly understood, and there is no effective treatment to prevent its progression. Based on results from animal and clinical studies, certain neuronal-humoral factors (NHFs), such as IGF-1, dopamine, and cortisol may be involved in the progression of pediatric myopia. Digital therapeutics uses evidence-based software as therapeutic interventions and it has the potential to offer innovative treatment strategies for pediatric myopia beyond conventional treatment methods. In this perspective article, we introduce digital therapeutics SAT-001, a software algorithm that modulates the level of NHFs to reduce the progression of pediatric myopia. The proposed mechanism is based on a theoretical hypothesis derived from scientific research and clinical studies and will be further confirmed by evidence generated from clinical studies involving pediatric myopia.

ISNT rule satisfaction in Korean non-glaucomatous subjects.

PURPOSE: To evaluate the efficacy of the ISNT rule in normal eyes of Koreans. METHODS: We retrospectively reviewed medical records of 890 subjects with fundus photographs and evaluated the presence of the cup and ISNT rule satisfaction. If the ISNT rule was violated, the quadrants in which the neuroretinal rim was thinnest and thickest, respectively, were evaluated. RESULTS: Among 890 eyes, 84.7% showed the cup. The subjects without the cup were significantly younger and more hyperopic. Among 754 eyes with the cup, 53.5% showed ISNT rule satisfaction. In 351 eyes violating the ISNT rule, the most common quadrant showing the thickest neuroretinal rim was the inferior (65.5%), and the thinnest, the temporal (98.3%). CONCLUSION: The cup was absent in 15% of the assessed eyes. Only about half of eyes with the cup showed ISNT rule satisfaction. Even in eyes violating ISNT rule, the inferior was the most common quadrant with the thickest neuroretinal rim and the temporal, the thinnest.

Serum Biomarkers for the Diagnosis of Glaucoma.

Despite the importance of the early detection of glaucoma, most patients with progressive glaucoma show minimal symptoms. We aimed to evaluate biomarkers for glaucoma diagnosis in Korea. Forty-two volunteers with/without open-angle glaucoma were enrolled from January through October 2015-divided into a control or open-angle glaucoma group, which was further divided into normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) groups-and underwent assessments for myelin basic protein (MBP), heat shock protein 60, anti-Sjögren's-syndrome-related antigen A (SSA) and antigen B (SSB), anti-α-fodrin, and anti-nucleic acid. The glaucoma group showed a higher serum MBP level and lower serum anti-α-fodrin antibody level than the control group (p < 0.05). The NTG group showed higher serum anti-SSA and anti-SSB levels and lower anti-α-fodrin IgG/IgA levels than the HTG group. In the receiver operating characteristic curve analysis, the area under the curve (AUC) for serum MBP level was 0.917 in discriminating between controls and patients with glaucoma. Between the NTG and HTG groups, anti-SSA, anti-SSB, and anti-α-fodrin IgG/IgA levels showed an AUC above 0.8. Thus, these biomarkers were useful for diagnosing glaucoma and discriminating between controls and patients with glaucoma, and patients with NTG and HTG.

Utility of the optical quality analysis system for decision-making in cataract surgery.

BACKGROUND: A cataract is a common cause of vision impairment that requires surgery in older subjects. The Optical Quality Analysis System (OQAS, Visiometrics SL, Terrassa, Spain) assesses the optical quality of the eye in cataract patients. This study shows the role of the optical quality evaluation system for decision-making in cataract surgery. We investigated the clinical utility of the OQAS for decision-making in cataract surgery. METHODS: Sixty-seven eyes from 67 patients undergoing cataract surgery and 109 eyes from 109 control subjects were compared. The best corrected visual acuity (BCVA) was measured. The objective scatter index (OSI), modulation transfer function (MTF), Strehl ratio, predicted visual acuity (PVA) 100%, PVA 20%, and PVA 10% were measured using the OQAS. The sensitivity and specificity of the different parameters were analyzed using the receiver operating characteristic (ROC) curve. The main parameters measured were sensitivity and specificity. RESULTS: The BCVA, OSI, PVA 100%, PVA 20%, and PVA 10% were higher in the cataract group compared to those in the control group, while the MTF and Strehl ratios were lower (p <  0.001 for all). ROC analysis showed that the OSI had the largest area under the curve and that the sensitivity and specificity of the OSI were 83.9 and 84.6%, respectively, at the optimal cut-off point of 2.35. CONCLUSION: The MTF, OSI, Strehl ratio, PVA 100%, PVA 20% and PVA 10% may be useful parameters for preoperative decision-making in cataract surgery. The OSI appears to be the most effective parameter for this purpose.

Influence of Myopia on Size of Optic Nerve Head and Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography.

PURPOSE: To investigate optic nerve head size and retinal nerve fiber layer (RNFL) thickness according to refractive status and axial length. METHODS: In a cross-sectional study, 252 eyes of 252 healthy volunteers underwent ocular biometry measurement as well as optic nerve head and RNFL imaging by spectral-domain optical coherence tomography. Correlation and linear regression analyses were performed for all subjects. The magnification effect was adjusted by the modified axial length method. RESULTS: Disc area and spherical equivalent were positively correlated (r = 0.225, r2 = 0.051, p = 0.000). RNFL thickness showed significant correlations with spherical equivalent (r = 0.359, r2 = 0.129, p = 0.000), axial length (r = -0.262, r2 = 0.069, p = 0.000), disc radius (r = 0.359, r2 = 0.129, p = 0.000), and radius of the scan circle (r = -0.262, r2 = 0.069, p = 0.000). After adjustment for the magnification effect, those relationships were reversed; RNFL thickness showed negative correlation with spherical equivalent and disc radius, and positive correlation with axial length and radius of the scan circle. The distance between the disc margin and the scan circle was closely correlated with RNFL thickness (r = -0.359, r2 = 0.129, p = 0.000), which showed a negative correlation with axial length (r = -0.262, r2 = 0.069, p = 0.000). CONCLUSIONS: Optic disc radius and RNFL thickness decreased in more severely myopic eyes, but they increased after adjustment for magnification effect. The error due to the magnification effect and optic nerve head size difference might be factors that should be considered when interpreting optical coherence tomography results.

Comparison of Intraocular Pressure Measurements Obtained by Rebound, Noncontact, and Goldmann Applanation Tonometry in Children.

PURPOSE: To compare intraocular pressure (IOP) among rebound, noncontact, and Goldmann applanation tonometry (GAT) and their relationships to central corneal thickness in children. DESIGN: Diagnostic protocol comparison and evaluation. METHODS: In right eyes of 419 children, mean IOP, rates of successful measurement with 3 tonometries, and intermethod agreement by Bland-Altman plot were assessed. The influences of central corneal thickness, and of average IOP of 3 tonometries on IOP differences between tonometries, were evaluated. RESULTS: The mean age was 8.89 ± 3.41 years (3-15 years). There was significant difference in mean IOP of each tonometry; GAT showed the lowest values (P < .05). The IOP was successfully measured by noncontact tonometry in 89%, by rebound tonometry in 75%, and by GAT in 64% of children less than 10 years old, and in 100%, 98%, and 94% of children older than 10 years, respectively. The IOP of each tonometer positively correlated with central corneal thickness (P < .05). The mean differences and limits of agreement were 0.81 ± 6.19 mm Hg (noncontact minus rebound), 2.56 ± 4.62 mm Hg (rebound minus GAT), and 1.81 ± 4.76 mm Hg (noncontact minus GAT). Rebound and noncontact tonometry overestimated IOP relative to GAT for thicker central corneal thicknesses. Rebound tonometry overestimated IOP relative to GAT and noncontact tonometry at higher average IOP of 3 tonometries. CONCLUSIONS: Rebound, noncontact, and Goldmann applanation tonometries can be considered appropriate methods for children, though noncontact tonometry is the most accessible. Given the risk of false-positive diagnosis of pediatric glaucoma, attention should be devoted to children with IOP within a suspicious range or thicker cornea.

Stemness characteristics of human corneal endothelial cells cultured in various media.

PURPOSE: To investigate stemness characteristics of human corneal endothelial cells (HCECs) cultured in various media. METHODS: Human corneal endothelial cells were isolated using a sphere-forming assay. Cells were allowed to attach to the bottom of culture plates and were cultured in different media designated as medium A (Opti-MEM I with 8% fetal bovine serum), medium B (DMEM/F12 with B27 supplement), medium E (DMEM/F12 with epidermal growth factor [EGF]), and medium BE (DMEM/F12 with B27 supplement and EGF), respectively. Cell morphology was evaluated with an phase-contrast inverted microscope. Immunofluorescence staining and western blotting of nestin, octamer-binding transcription factor (OCT3/4), glial fibrillary acidic protein (GFAP), zonula occludens-1 (ZO-1), collagen VIII alpha2, and Na-K ATPase was performed. Cell proliferation was assessed with a cell counting kit-8 assay. RESULTS: A few cultured cells stained with nestin. The cells cultured in medium A expressed high levels of GFAP, OCT3/4, and nestin, and higher levels of ZO-1 were expressed in the cells cultured in medium A and medium B compared with cells cultured in the other media. The cells cultured in medium A assumed a fibroblast-like shape, whereas the cells cultured in medium B and medium BE appeared as mosaics. Cell proliferation was highest in medium A compared with those cultured in the other media. CONCLUSIONS: Cultured HCECs expressed stem cell markers, including nestin, OCT3/4, and GFAP. The expression of stem cell markers differed according to the culture media and associated proliferation rate.

The effects of different culture media on human corneal endothelial cells.

PURPOSE: To investigate the most appropriate media condition for the proliferation and functional maintenance of human corneal endothelial cells (HCECs). METHODS: We cultured HCECs in traditional media (medium A or D) and in stem cell media (medium E or N). The morphology of the cells was evaluated by inverted microscopy. Collagen, type VIII, alpha 2 and sodium-potassium adenosine triphosphatase (Na(+)-K(+) ATPase) expression were analyzed as differentiation markers. Octamer-binding transcription factor 3/4, glial fibrillary acidic protein, nestin and ß-catenin expression were evaluated as stem cell associated proteins. The cell proliferation rate was evaluated with a cell counting kit-8 assay. Wound healing assays were also performed. The transendothelial electrical potential difference (TEPD) value was used to estimate the endothelial cell permeability in vitro. RESULTS: The proliferation and morphology analyses demonstrated that there were significant differences between the media. The expression of differentiation markers and stem cell-associated proteins was different between the media. Medium D resulted in higher proliferation rates compared with the other media, while still maintaining the differentiation potential and surface marker expression profile characteristic of HCECs. Compared with other media, TEPD was higher in medium N. CONCLUSIONS: Culture medium D was superior to the other media with regard to the expression of stem cell-associated proteins, proliferation, and cell migration. However, medium N was more appropriate than the other three media with regard to maintaining the proper cell shape and function.

Does intravitreal injections of bevacizumab for age-related macular degeneration affect long-term intraocular pressure?

PURPOSE: To evaluate the long-term intraocular pressure (IOP) changes after intravitreal injection of bevacizumab for age-related macular degeneration. PATIENTS AND METHODS: A total of 83 eyes that received intravitreal injections of bevacizumab for age-related macular degeneration were enrolled. IOP measurements at baseline, 6, 12, 18, and 24 months, and at the last follow-up after injection were analyzed. On the basis of the median number of injections, the changes in IOP were compared. RESULTS: The mean number of injections was 3.71±1.62. There was no significantly higher elevation than baseline IOP (14.11±2.76 mm Hg) after multiple intravitreal injections of bevacizumab (P>0.05). In the group which had ≥4 injections, mean IOP measurements were not higher compared with the group which had <4 injections during the follow-up period (P>0.05). In the patients with preexisting glaucoma (3 eyes), there were no significant increases of IOP during the follow-up period. CONCLUSIONS: IOP elevation was not observed during the long-term follow-up period. In addition, the numbers of injection and preexisting glaucoma did not affect IOP changes.

Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-ß1/ERK pathways regulation.

PURPOSE: To investigate the protective effect of rapamycin against alkali burn-induced corneal damage in mice. METHODS: BALB/c mice were treated with 0.1 N NaOH to the cornea for 30 seconds. Corneal neovascularization and opacity were clinically evaluated at 1, 2, and 4 weeks after chemical burn injury. Rapamycin was delivered topically to right eyes (1 mg/mL) and injected intraperitoneally (0.2 mg/kg) once a day. Concentrations of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-ß1) in the cornea were measured by enzyme-linked immunosorbent assay (ELISA). In vitro-cultured human corneal stromal cells were treated with 0 to 500 nM rapamycin for 3 days and then assessed by immunofluorescence staining of vimentin and alpha-smooth muscle actin (α-SMA). Western blotting assays for α-SMA, phosphorylated extracellular signal-regulated kinase (ρ-ERK 1/2), and total ERK 1/2 were also performed. RESULTS: Corneal neovascularization and corneal opacity scores measured 4 weeks after the chemical burn corneal injury were lower in the rapamycin group than in the control group. Two weeks after the chemical burn injury, a significant elevation in the corneal IL-6 levels of the positive control group was observed, compared to the levels in the negative control group or the rapamycin group (P < 0.05). Corneal TGF-ß1 levels were lower in the rapamycin-treated group than in the control group at 4 weeks after chemical burn injury (P < 0.05). Moreover, rapamycin inhibited TGF-ß1-induced α-SMA expression and augmented ERK 1/2 phosphorylation. CONCLUSIONS: Rapamycin treatment reduced corneal opacity and corneal neovascularization in BALB/c mice. Rapamycin protected the cornea from chemical damage via reduction of IL-6 and TGF-ß1 expression. Rapamycin reduced α-SMA expression through the ERK 1/2 pathway.

Intraocular pressure measured with Goldmann, noncontact, Schiøtz, and dynamic contour tonometry after DSEK.

PURPOSE: To compare intraocular pressure (IOP) measurements with various tonometers after Descemet stripping with endothelial keratoplasty (DSEK) and to measure the change in IOP during the follow-up period. METHODS: A total of 28 eyes of 28 patients having undergone DSEK for bullous keratopathy by a single surgeon from June 2008 to November 2011 were enrolled in this study. IOP values, which were measured with Goldmann applanation tonometry (GAT), noncontact tonometry (NCT), Schiøtz indentation tonometry (SIT), and dynamic contour tonometry, and central corneal thickness values were reviewed and analyzed up to 3 years after DSEK (range, 1 months-3 years). RESULTS: Different tonometers measured the IOP after DSEK differently. NCT showed the lowest IOP values, although GAT and NCT showed the smallest intertonometry difference. SIT showed extreme variation in IOP measurements. The dynamic contour tonometry values were higher than those of NCT or GAT. Central corneal thickness did not correlate with any of the IOP measurements. Only 2 episodes of IOP elevation greater than 30 mm Hg were detected. CONCLUSIONS: IOP measured with NCT or GAT may be lower than the real IOP after DSEK. SIT is not a reliable tonometry measurement after DSEK. Additional IOP measurements using different methods and consideration of other clinical signs may be the best method for ocular evaluation after DSEK.

Are ocular complications of a high-dose glucocorticoid treatment appropriately monitored in patients with rheumatic diseases?

Glucocorticoid is frequently used in treating various rheumatic conditions. However it is known to cause multiple toxicities including cataract or glaucoma. In this study, we examined whether patients with rheumatic diseases had appropriate ocular monitoring for glucocorticoid toxicities. From rheumatology clinics in South New Jersey of the USA, we retrospectively identified patients with ages between 18 and 60 years old who received a high accumulative dose of glucocorticoid, which was defined as glucocorticoid dose greater than prednisone 7.5mg/day × 6 months = 1,350 mg. We observed rheumatologists recommended eye examinations only in 14/37 (37.8 %) of patients. Family history was present for cataract in 13/37 (35.1 %) patients and for glaucoma in 6/37 (16.2 %) patients. Rheumatologists recommended eye examinations in 4/13 (30.7 %) and 0/6 (0 %) patients in each group. This study suggested that rheumatologists did not appropriately monitor ocular complications of a high dose glucocorticoid, even in patients with a positive family history.

Chemically injured keratocytes induce cytokine release by human peripheral mononuclear cells.

PURPOSE: To establish an in vitro model to study the role of keratocytes in corneal chemical burns and to investigate the interaction between chemically injured keratocytes and human peripheral blood mononuclear cells (PBMCs). METHODS: Human keratocytes, epithelial cells, and PBMCs were cultured. The PBMC stimulation assay was then performed using cultured human keratocytes, epithelial cells, and NaOH-treated keratocytes. Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-ß1), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA. RESULTS: Human keratocytes stimulated PBMC proliferation (p=0.016), and keratocytes treated with various concentrations of NaOH further stimulated PBMC proliferation compared to control cells in a dose-dependent manner (p=0.028 and 0.009). MMP-9 and MIF levels were higher than in the negative controls, while TGF-ß1 levels did not differ from those of the negative controls. CONCLUSION: Our results suggest that PBMCs are stimulated by chemically injured keratocytes, and produce inflammatory cytokines in response. This may be a major mechanism underlying the process causing corneal chemical burn injuries. This model can be used as an in vitro model for further studies on corneal chemical burns.

Oral alcohol administration disturbs tear film and ocular surface.

PURPOSE: To investigate whether ethanol administration disturbs the tear film and ocular surface. DESIGN: Case-control study. PARTICIPANTS: Twenty healthy male subjects were recruited. Ethanol was administered to 10 subjects and another 10 subjects served as controls. METHODS: Twenty healthy male subjects with no ocular disease were recruited. Ethanol (0.75 g/kg) was administered orally at 8 pm for 2 hours to 10 subjects. MAIN OUTCOME MEASURES: The tear film and ocular surface were evaluated at 6 pm before drinking, at midnight, and immediately (6 am) and 2 hours (8 am) after waking the next morning. Tear osmolarity, ethanol concentration in tears and serum, Schirmer's test results, tear film break-up time (TBUT), corneal punctuate erosion, and corneal sensitivity were measured. RESULTS: Ethanol was detected in tears and serum at midnight, but it was not detected the next morning. The mean tear osmolarity level increased in the alcohol group at midnight compared with that in the control group (P<0.001). The alcohol group showed a significantly shorter TBUT compared with the control group after drinking alcohol (P<0.001 at 12 am, P<0.001 at 6 am, and P = 0.002 at 8 am). There were significantly higher fluorescein staining scores in the alcohol group compared with those in the control group at 6 am and 8 am (P = 0.001 and P<0.001, respectively). No significant change was shown in corneal sensitivity or Schirmer's test results in either group. CONCLUSIONS: Orally administered ethanol was secreted into the tears. Ethanol in tears induced tear hyperosmolarity and shortened TBUT and triggered the development of ocular surface diseases. Similar changes could exacerbate signs and symptoms in patients with ocular surface disease.

Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells - chemically injured keratocyte reaction.

PURPOSE: To investigate the effect of antioxidants and immunosuppresants on mixed peripheral blood mononuclear cells (PBMC) - chemically injured keratocytes reaction (MLKR). METHODS: The PBMC stimulation assay was performed using chemically injured keratocytes treated with 0.05 N NaOH for 90 s (MLKR). MLKR were treated with various drugs including rapamycin, dexamethasone, mycophenoleic acid (MPA), alpha lipoic acid (ALA), and N-acetyl cysteine (NAC). Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-ß1), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA. RESULTS: Anti-oxidants as well as immunosuppressants suppressed PBMC proliferation. MMP-9 levels were lower in antioxidants group. IL-6 levels decreased in dexamethasone group and anti-oxidants group. Combination of immunosuppressants and antioxidants suppressed more PBMC proliferation except for rapamycin + ALA group, suppressed MMP-9 production except for MPA + ALA group, decreased IL-6 levels and increased MIF levels except for rapamycin + ALA group. TGF-ß1 levels were elevated in rapamycin group and rapamycin + ALA group. CONCLUSIONS: Cytokine production was different depending on combination of drugs.Our results suggest that the different drugs should be selected for treatment according to the phases of corneal chemical burn.

Peripapillary retinal thickness maps in the evaluation of glaucoma patients: a novel concept.

Purpose. To show how peripapillary spectral domain optical coherence tomography (SDOCT) retinal thickness (RT) maps can complement retinal nerve fiber layer (RNFL) thickness maps in the evaluation of glaucoma patients. Methods. After a complete eye exam with standard fundus photography and visual field testing, normal and glaucomatous eyes were imaged with an experimental SDOCT system. From SDOCT images, RNFL thickness and RT maps were constructed and then correlated with disc photography and visual field testing. Results. Two normal eyes of 2 patients and 5 eyes of 4 glaucoma patients were imaged. Although both RNFL and RT maps correlated well with visual field defects, glaucomatous arcuate defects were sometimes more easily identified in the RT maps. Conclusions. To our knowledge, this is the first paper to show that peripapillary SDOCT RT maps may provide important supplemental information to RNFL thickness maps in the evaluation of glaucoma patients.

Imaging of optic nerve head drusen: improvements with spectral domain optical coherence tomography.

OBJECTIVE: To demonstrate a new algorithm that can determine the shape, location, and volume of optic nerve head drusen (ONHD), which were imaged with spectral domain optical coherence tomography (SDOCT). METHODS: One exenteration patient and 4 glaucoma patients with bilateral ONHD were recruited from the Massachusetts Eye and Ear Infirmary and from a private practice office. Images were obtained using an experimental SDOCT system developed at the Wellman Center for Photomedicine, Massachusetts General Hospital. With axial resolutions of about 6 mum, SDOCT can obtain 2-dimensional images in 1/29 of a second, compared with commercially available time domain OCT instruments with 10 mum resolution images in 1.28 seconds. The volumes of ONHD were calculated with a new algorithm and were then correlated with visual field mean deviation. RESULTS: SDOCT can display 2-dimensional images comparable with histology and 3-dimensional videos of ONHD. ONHD are signal-poor regions with high-signaled borders. Larger ONHD volumes are directly correlated with larger mean deviation absolute values on Humphrey visual field testing. CONCLUSIONS: SDOCT is a potentially better technique for ONHD imaging and may improve the diagnosis and management of patients with both OHND and glaucoma.