Preparation and Evaluation of Antimicrobial Properties and Cytotoxic Potentials of Nutmeg and Tulsi Gel.

AIM: The aim of the study is to prepare the dual gel using nutmeg and Tulsi and then the evaluation of the antimicrobial properties and cytotoxic potential. MATERIALS AND METHODS: The Nutmeg Tulsi gel preparation has been done with a mixture of equal amounts of nutmeg and Tulsi powder. To the above-mentioned mixture, 5 mL of the concentrate is added and mixed thoroughly until the gel formation is done. The antimicrobial property is checked in the Porphyromonas gingivalis organism (p>0.05). The cytotoxic potential is checked in the Brine variety of the shrimp. The statistical analysis is done using a Paired t-test. RESULTS: The results stated that the Nutmeg Tulsi gel at a concentration of 100 microgram/mL showed a greater zone of inhibition (4.1±0.09 mm) when compared with doxycycline and has high antimicrobial potential in both Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Conclusion: The antimicrobial property of Nutmeg Tulsi gel has been demonstrated to be effective against P. gingivalis and A. actinomycetemcomitans. This suggests that it could be used as an affordable and effective "adjunct" alongside standard care for managing periodontal conditions.

A comprehensive update on the use of optical coherence tomography angiography in glaucoma.

PURPOSE: The primary purpose of this review is to provide a comprehensive summary on the technical principles of OCTA and to enumerate vascular parameters being explicated for glaucoma diagnosis and progression with emphasis on recent studies. In addition, the authors also summarize the future clinical potentials of OCTA in glaucoma and enumerate the limitations of this imaging modality in the present-day scenario. METHODS: The index study is a narrative review on OCTA in glaucoma. The authors searched the PubMed database using the key phrases ''optical coherence tomography angiography" AND "glaucoma,'' AND/OR "vascular parameters" AND/OR "ocular perfusion." Being a relatively recent development in ocular imaging, studies in which OCTA imaging had been used for glaucoma evaluation since 2012 were included until March 2022. The literature search included original studies and previous review articles, while case reports were excluded. Preliminary search was based on relevant articles with search keywords in the title and abstract. The second screening was performed by reading the full text of the literature. RESULTS: Recent studies indicate reduction in microcirculation in glaucomatous eyes compared to the normal subjects. The area of interest for glaucoma evaluation using OCTA varies among the different studies. Based on the literature reviewed here, (1) OCTA parameters measured in the peripapillary; ONH and macular area have been shown to differentiate between glaucoma and normal eyes with a discriminatory power comparable to OCT parameters used routinely in clinics, (2) monitoring of peripapillary and macular vessel density may provide important information to the evaluation of glaucoma progression and prediction of rates of disease worsening, (3) studies suggest strong correlation between the OCTA parameters, the OCT parameters and visual function, measured by visual field testing, in glaucomatous eyes, (4) future prospects of OCTA in glaucoma evaluations using AI predicting structural and functional features and prognosis based on early vascular findings would open up scope for early detection of high-risk suspects and fast progressors in glaucoma. CONCLUSION: OCTA can be useful in quantifying vascular parameters in the optic disc, peripapillary and the macular regions for glaucoma evaluation. OCTA shows potential to become a part of everyday glaucoma management.

Diagnostic Accuracy of Frequency-Doubling Technology and the Moorfields Motion Displacement Test for Glaucoma.

PURPOSE: Portable perimetric testing could be useful for community-based glaucoma screening programs. Frequency-doubling technology (FDT) and the Moorfields motion displacement test (MDT) are portable perimeters that have shown promise as potential screening tools for glaucoma. This study's goal was to determine the diagnostic accuracy of FDT and MDT for visual field defects and glaucoma. DESIGN: Prospective, cross-sectional, diagnostic accuracy study. PARTICIPANTS: A consecutive series of patients aged ≥ 50 years who presented to a glaucoma clinic in South India and had never undergone Humphrey field analyzer (HFA) visual field testing in the past. METHODS: Participants underwent 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard HFA perimetry, FDT perimetry, MDT perimetry, and iPad perimetry using visualFields Easy in random order. Ophthalmologist grades of HFA and optic nerve head photographs were used as reference standards for glaucoma and field defect presence. Receiver operating characteristic curves were constructed to assess the diagnostic accuracy of various parameters for each test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). RESULTS: Overall, 292 eyes from 173 participants were included, with 112 eyes classified as moderate or worse glaucoma. For moderate or worse glaucoma detection, the best parameter on FDT was mean deviation (MD) (AUROC, 0.84; 95% confidence interval [CI], 0.79-0.89) and the best parameter on MDT was global probability of true damage (GPTD) (AUROC, 0.87; 95% CI, 0.82-0.91). When specificity was set to 90%, the sensitivity for detection of moderate or worse glaucoma was 55% (95% CI, 39%-68%) for FDT MD and 62% (95% CI 52%-71%) for MDT GPTD. CONCLUSIONS: Frequency-doubling technology and MDT perimetry had fair diagnostic accuracy for glaucoma detection when administered to naïve test takers in this South Indian population. Although not appropriate for use as a sole glaucoma screening test, these perimetric tests may be useful as ancillary tests. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Diagnostic accuracy of an iPad application for detection of visual field defects.

BACKGROUND/OBJECTIVES: Tablet-based perimetry could be used to test for glaucomatous visual field defects in settings without easy access to perimeters, although few studies have assessed diagnostic accuracy of tablet-based tests. The goal of this study was to determine the diagnostic accuracy of iPad perimetry using the visualFields Easy application. SUBJECTS/METHODS: This was a prospective, cross-sectional study of patients undergoing their first Humphrey Field Analyser (HFA) visual field test at a glaucoma clinic in India. Participants underwent 24-2 SITA Standard HFA testing and iPad-based perimetry with the visualFields Easy application. Reference standards for both visual field loss and suspected glaucoma were determined by ophthalmologist review of HFA results and optic disc photographs. Receiver operating characteristic curves were constructed to assess diagnostic accuracy at various test thresholds. RESULTS: 203 eyes from 115 participants were included, with 82 eyes classified as moderate or worse glaucoma. iPad perimetry had an area under the receiver operating characteristic (AUROC) curve of 0.64 (95% CI 0.57 to 0.71) for detection of any visual field defect relative to HFA and an AUROC of 0.68 (0.59 to 0.76) for detection of moderate or worse glaucoma relative to ophthalmologist examination. At a set specificity of 90%, the sensitivity of iPad perimetry for detection of moderate or worse glaucoma was 35% (22-48%). CONCLUSIONS: iPad perimetry using the visualFields Easy application had inadequate diagnostic accuracy to be used as a screening tool for glaucoma in this South Indian population.

Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study.

AIM: To assess the potential for systemic toxicity when silver nanoparticle-coated mini-implants were implanted in Wistar albino rats conducted as a comparative study in the animal model by assessing the blood biochemistry, liver and kidney function, and histology of the implanted site. MATERIALS AND METHODS: The surface of the mini-implant was coated with a green-mediated silver nanoparticle. Uncoated mini-implants were placed in two groups of eight Wistar albino rats, and silver nanoparticle-coated mini-implants were placed in another eight rats. The bone's general conditions, blood biochemistry assessing for ALT, AST, GPT, GOT, and histological sections using H and E stain and Masson's Trichrome stain were examined at 7, 14, and 28-day intervals. RESULTS: The creatinine, urea, ALP, and ALT showed no signs of systemic toxicity during the 28-day follow-up period in the Wistar rats both in the test and control groups. The histological evaluation, which was conducted using HE and MTS stain, revealed osteogenesis and adequate healing of the insertion site in the group where coated mini-implant was placed. The bone sample revealed no abnormalities in the control group with uncoated mini-implants. CONCLUSION: Green synthesized silver nanoparticle-coated mini-implant does not cause systemic toxicity as indicated by no abnormalities in the levels of creatinine, urea, ALT, ALP, GPT, and GOT. The bone histology indicates that the coated mini-implants placed in animal bone healed with adequate osteogenesis. CLINICAL SIGNIFICANCE: Silver nanoparticles have potential for antimicrobial activity. Mini-implants placed as temporary anchorage devices in orthodontics often fail due to inflammation and plaque. Silver nanoparticle-coated mini-implants would reduce the risk of mini-implant failure as it would have antimicrobial potential and eliminate this cause for failure of mini-implants. How to cite this article: Sreenivasagan S, Subramanian AK, Mohanraj KG, et al. Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study. J Contemp Dent Pract 2023;24(12):944-950.

Comparison of Structural, Functional, Tonometric, and Visual Acuity Testing for Glaucoma: A Prospective Diagnostic Accuracy Study.

PURPOSE: To determine the diagnostic accuracy of potential screening tests for moderate to advanced glaucoma. DESIGN: Prospective diagnostic test accuracy study. PARTICIPANTS: The study enrolled a consecutive series of patients aged ≥50 years who presented to a glaucoma clinic in South India without ever having received automated visual field testing. METHODS: All participants underwent 8 index tests: OCT of the peripapillary retinal nerve fiber layer, optic disc photography, Moorfield's Motion Displacement Test (MDT), frequency doubling technique perimetry, noncontact tonometry, pneumatonometry, presenting visual acuity, and best-corrected visual acuity. Participants also underwent stereoscopic photographs and Humphrey visual fields, which were used by 2 ophthalmologists to arrive at the reference standard diagnosis of moderate to advanced glaucoma. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. RESULTS: A total of 217 people were enrolled; 321 eyes from 180 participants had all tests performed. Of these, 127 eyes (40%) were classified as having moderate to advanced glaucoma. Among the 8 tests, OCT best optimized sensitivity (84%, 95% confidence interval [CI], 76-90) and specificity (75%, 95% CI, 68-81). Moorfield's Motion Displacement Test was the best perimetric test, with a sensitivity of 91% (95% CI, 85-96) and specificity of 53% (95% CI, 44-61). Pressure and vision tests were not sensitive (e.g., sensitivity of 16%, 95% CI, 9-23 for noncontact tonometry and 23%, 95% CI, 15-31 for best-corrected visual acuity). Moorfield's Motion Displacement Test identified 16 of 127 eyes (13%) with glaucoma that were not captured by OCT, but also had false-positive results in 65 of 194 eyes (34%) without glaucoma that OCT correctly classified as negative. CONCLUSIONS: OCT had moderate sensitivity and fair specificity for diagnosing moderate to advanced glaucoma and should be prioritized during an initial assessment for glaucoma.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

Accuracy of autorefraction in an adult Indian population.

PURPOSE: Autorefractors allow non-specialists to quickly assess refractive error, and thus could be a useful component of large-scale vision screening programs. In order to better characterize the role of autorefraction for public health outreach programs in resource-limited settings, the diagnostic accuracy of two autorefractors was assessed relative to subjective refraction in an adult Indian population. METHODS: An optometrist refracted a series of patients aged ≥50 years at an eye clinic in Bangalore, India using the Nidek ARK-900 autorefractor first, followed by the 3nethra Royal autorefractor, and then subjective refraction. The diagnostic accuracy of each autorefractor for myopia, hyperopia, and astigmatism was assessed using subjective refraction as the reference standard, and measures of agreement between refractions were calculated. RESULTS: A total of 197 eyes in 104 individuals (mean age 63 ± 8 years, 52% female) were evaluated. Both autorefractors produced spherical equivalent estimates that were on average more hyperopic than subjective refraction, with a measurement bias of +0.16 D (95%CI +0.09 to +0.23D) for Nidek and +0.42 D (95%CI +0.28 to +0.54D) for 3nethra. When comparing pairs of measurements from autorefraction and subjective refraction, the limits of agreement were approximately ±1D for the Nidek autorefractor and ±1.75D for the 3Nethra autorefractor. The sensitivity and specificity of detecting ≥1 diopter of myopia were 94.6% (95%CI 86.8-100%) and 92.5% (95%CI 88.9-97.5%) for the Nidek, and 89.2% (95%CI 66.7-97.4) and 77.5% (95%CI 71.2-99.4%) for the 3Nethra. The accuracy of each autorefractor increased at greater levels of refractive error. CONCLUSIONS: The sensitivity and specificity of the Nidek autorefractor for diagnosing refractive error among adults ≥50 years in an urban Indian clinic was sufficient for screening for visually significant refractive errors, although the relatively wide limits of agreement suggest that subjective refinement of the eyeglasses prescription would still be necessary.

Evaluation of anterior chamber angle by van Herick grading and ultrasound biomicroscopy in light and dark conditions for finding appositional angle closure and plateau iris configuration.

PURPOSE: To evaluate association of the van Herick (VH) grades with the ultrasound biomicroscopic (UBM) parameters, appositional irido-trabecular contact (A-ITC) and plateau iris (PI) in a randomly sampled population. METHODS: A 10% random sample of all residents aged 40 or older of the Kumejima study underwent UBM under dark and light conditions in the four quadrants of right eyes. RESULTS: Of 301 right eyes with eligible UBM images, 101 (33.6%) and 200 (66.4%) were classified as VH ≤ 2 and VH ≥ 3, respectively. The UBM parameters on angle width and ciliary body configuration were significantly different between VH ≤ 2 and VH ≥ 3 eyes (p < 0.001). A-ITC was found in at least one quadrant in 54.5% and 75.2% of VH ≤ 2 eyes under light and dark conditions, respectively; and 20.5% and 45.5% of VH ≥ 3 eyes. When 'VH ≤ 2' was used to screen eyes with A-ITC in three or more quadrants, the sensitivity and specificity were 74.1% and 75.3%, respectively. A-ITC was significantly associated with shallower anterior chamber (p = 0.018) and higher intraocular pressure (p = 0.044) in VH ≥ 3 eyes. Plateau iris (PI) was found in 15.8% and 6.0% of VH ≤ 2 and VH ≥ 3 eyes, respectively. Plateau iris (PI) was significantly associated with the UBM parameters on angle width and ciliary body configuration. When 'VH ≤ 2' was used to screen eyes with PI, the sensitivity and specificity were 57.1% and 68.9%, respectively. CONCLUSIONS: The VH grade of ≤2 and ≥3 showed significant association with UBM angle width and ciliary body configuration parameters. The VH ≤ 2 criterion should be useful for screening of A-ITC and PI.

Reproducibility of 5 Methods of Ocular Tonometry.

PURPOSE: To evaluate the agreement between Goldmann applanation tonometry (GAT; Haag-Streit, Bern, Switzerland) and several portable tonometers that could be used for glaucoma screening programs. DESIGN: Evaluation of a diagnostic test. PARTICIPANTS: Three hundred twenty-one eyes of 168 participants seeking treatment at the glaucoma clinic of a tertiary eye hospital in India. METHODS: Participants underwent intraocular pressure (IOP) measurement with GAT and 4 index tests: the Icare TA01i rebound tonometer (Icare USA, Raleigh, NC), a noncontact tonometer (NCT; Topcon CT-80; Topcon; Tokyo, Japan), a pneumatonometer (Model 30; Reichert Technologies; Depew, NY), and the Tono-Pen AVIA (Reichert Technologies). MAIN OUTCOME MEASURES: Estimates of reproducibility of IOP measurements between each index test and GAT, including the intraclass correlation coefficient (ICC) and the Bland-Altman 95% limits of agreement. RESULTS: The Icare showed the greatest agreement with GAT (ICC, 0.69; 95% confidence interval, 0.61-0.74), followed by the NCT (ICC, 0.65; 95% confidence interval, 0.58-0.71), the Tono-Pen (ICC, 0.51; 95% confidence interval, 0.43-0.59), and the pneumatonometer (ICC, 0.36; 95% confidence interval, 0.27-0.44). The pneumatonometer and Tono-Pen tended to overestimate IOP relative to GAT, with a mean difference of 3.4 mmHg (95% limits of agreement [LOA], -7.3 to 14.1 mmHg) for the pneumatonometer and 3.2 mmHg (95% LOA, -6.1 to 12.6 mmHg) for the Tono-Pen. In contrast, measurements from the Icare and NCT were on average within 1 point of those for GAT (mean difference, -0.4 mmHg [95% LOA, -8.4 to 7.6 mmHg] and -0.5 mmHg [95% LOA, -8.7 to 7.6 mmHg], respectively). CONCLUSIONS: The Icare and NCT both demonstrated good agreement with GAT across a wide range of IOPs and could be considered for glaucoma screening programs.

Inverse Calculation of Composite Kink-Band Toughness from Open-Hole Compression Strength.

Fiber-reinforced polymer matrix composite materials can fail by kink-band propagation mechanism when subjected to in-plane compressive loading. This mode of failure is especially prevalent in compressive loading of laminates with holes, cut-outs, or impact damage. Most of the successful models for predicting compressive strength of such laminates require "fracture" toughness associated with kink-band propagation under in-plane compression. However, this property is difficult to measure experimentally, limiting the use of such models in design practice. In this paper an inverse method is proposed to estimate the kink-band toughness of the laminate from its open-hole compression strength data, which is an easier property to measure experimentally. Furthermore, a scaling relationship is proposed to estimate kink-band toughness for other laminate configurations of the same material.

Residual Angle Closure One Year After Laser Peripheral Iridotomy in Primary Angle Closure Suspects.

PURPOSE: To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS). DESIGN: Subanalysis of randomized controlled trial data. METHODS: AS-OCT images from 181 PACS subjects ≥50 years of age were analyzed using customized software before and 1 year after LPI. Other parameters assessed were intraocular pressure (IOP) and axial length (Axl). Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI. Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI. RESULTS: The mean age of participants was 62.4 (standard deviation 9.9) years. The majority were female (137, 75.7%) and Chinese (174, 96.1%). At 1 year post LPI, 148 (81.8%) subjects had gonioscopic residual angle closure. Univariate analysis showed that baseline Axl, anterior chamber area, anterior chamber volume, angle opening distance at 750 µm from the scleral spur, and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects (all P < .05). Multivariate analysis revealed that baseline iris volume (B = -0.08, P = .035) and baseline IOP (B = 0.23, P = .032) were predictors for residual angle closure. CONCLUSIONS: One year after LPI, >80% of PACS had gonioscopic residual angle closure. Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure.

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Association of iris crypts with acute primary angle closure.

PURPOSE: To determine the relationship between iris surface features and acute primary angle closure (APAC) in eyes with angle closure. DESIGN: Case-control study involving Asian patients diagnosed with previous APAC, primary angle closure suspect (PACS), primary angle closure (PAC) and primary angle closure glaucoma (PACG) at an eye centre in Singapore between August 2012 and January 2015. METHODS: Participants underwent ophthalmic examination and digital slit-lamp iris photography. Iris surface features were graded based on crypts, furrows and colour. Fellow eyes of APAC were compared with PACS and PAC/PACG eyes with regard to their iris surface features. MAIN OUTCOME MEASURE: Occurrence of APAC. RESULTS: A total of 309 patients (71 APAC, 139 PACS, 47 PAC and 52 PACG) were included (mean age: 67.7±7.2 years and 36.6% male). Compared with PACS, higher crypt grade was significantly associated with lower odds of APAC (OR=0.58 for one grade higher in crypt grade; p=0.027, adjusted for age, gender, ethnicity and pupil diameter). The results remained similar when compared with PAC/PACG group (OR=0.58 for one grade higher in crypt grade; p=0.043). We did not observe any significant associations between iris furrows or colour with presence of APAC. CONCLUSIONS: Our study comprising Asian eyes with angle closure suggests that the presence of a higher crypt grading may be protective for APAC. As such, assessing iris surface architecture for crypts could be a new measure for risk stratification of developing APAC in eyes with angle closure.

Diagnostic ability of peripapillary vessel density measurements of optical coherence tomography angiography in primary open-angle and angle-closure glaucoma.

AIMS: To evaluate the diagnostic ability of peripapillary vessel density measurements on optical coherence tomography angiography (OCTA) in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and to compare these with peripapillary retinal nerve fibre layer (RNFL) thickness measurements. METHODS: In a cross-sectional study, 48 eyes of 33 healthy control subjects, 63 eyes of 39 patients with POAG and 49 eyes of 32 patients with PACG underwent OCTA (RTVue-XR, Optovue, Fremont, California, USA) and RNFL imaging with spectral domain OCT. Diagnostic abilities of vessel density and RNFL parameters were evaluated using area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities. RESULTS: AUCs of peripapillary vessel density ranged between 0.48 for the temporal sector and 0.88 for the inferotemporal sector in POAG. The same in PACG ranged between 0.57 and 0.86. Sensitivities at 95% specificity ranged from 13% to 70% in POAG, and from 10% to 67% in PACG. AUCs of peripapillary RNFL thickness ranged between 0.51 for the temporal sector and 0.91 for the inferonasal sector in POAG. The same in PACG ranged between 0.61 and 0.87. Sensitivities at 95% specificity ranged from 8% to 68% in POAG, and from 2% to 67% in PACG. AUCs of all peripapillary vessel density measurements were comparable (p>0.05) to the corresponding RNFL thickness measurements in both POAG and PACG. CONCLUSIONS: Diagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density measurements were comparable to RNFL measurements in both POAG and PACG.

Discriminant Function of Optical Coherence Tomography Angiography to Determine Disease Severity in Glaucoma.

PURPOSE: To determine the discriminant function of optical coherence tomography angiography (OCTA) by disease severity in glaucoma. METHODS: In this prospective, observational cross-sectional study, all subjects underwent visual fields, retinal nerve fiber layer (RNFL) measurements, and OCTA imaging. Local fractal analysis was applied to OCTA images (radial peripapillary capillaries [RPC] layer). Vessel density en face and inside the disc and spacing between large and small vessels were quantified. Stepwise logistic regression was performed and a glaucoma severity score (range, 0-1: 0, normal; 1, severe glaucoma) was developed by using global and regional (superotemporal [ST], inferotemporal [IT], temporal, superonasal [SN], inferonasal, and nasal) vascular parameters. Glaucoma severity score was compared with visual field and RNFL indices. RESULTS: One hundred ninety-nine eyes (112 subjects) with glaucoma (28 eyes preperimetric; 83 early, 43 moderate, and 45 severe glaucoma) and 74 normal (54 subjects) eyes were enrolled. Preperimetric and glaucomatous eyes had significantly altered (P < 0.001) global vascular parameters as compared to normal; regionally, ST, then SN and IT sectors (in that order) showed more change in glaucomatous eyes. Vascular parameters showed better discriminant ability (area under the curve [AUC], sensitivity, and specificity of 0.70, 69.2%, and 72.9%, respectively) than structural parameters between normal and preperimetric glaucomatous eyes. Vascular parameters had comparable AUC (P > 0.05) to visual fields for perimetric glaucoma. Glaucoma severity score identified preperimetric glaucoma and early glaucoma better than did visual fields. CONCLUSIONS: Vascular parameters could be a useful adjunct tool to evaluate/diagnose glaucoma. Longitudinal studies are needed to determine their use in early detection and prognostication.

Short Pulse of Clinical Concentration of Bevacizumab Modulates Human Retinal Pigment Epithelial Functionality.

PURPOSE: Cross-talk between Notch signaling and vascular endothelial growth factor (VEGF) is a major driver of angiogenesis. Here we investigated the temporal effect of bevacizumab (BEV) on Notch signaling and the functional features of cultured primary retinal pigment epithelial (PRPE) cells. METHODS: Human (cadaver) PRPE cells were treated with clinical concentrations of BEV (0.25 mg/mL). Notch signaling pathway receptors, ligands, and downstream target genes were analyzed with quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation along with phagocytosis and transmembrane potential was analyzed by fluorescent activated cell sorter (FACS) and immunofluorescence. RESULTS: Bevacizumab-treated PRPE cultures revealed a significant temporal downregulation of notch4 (P < 0.05) and Delta-like-4 (P < 0.005) gene (16% reduced) and protein (29.7% reduced) expression only at the 2-hour exposure, though secreted VEGF levels were significantly blocked (P < 0.005) at all the time points (2, 4, 6 hours). Further, a significant downregulation (P < 0.005) in cell cycle (reduced by 34.1%) and a concurrent (P < 0.005) upregulation of F-actin staining (increased by 2.5-fold) could be detected. Bevacizumab-treated PRPE cells revealed an elevated transmembrane potential (by 63%) and significant decrease (P < 0.01) in phagocytosis (by 19.25%) in comparison to untreated controls. CONCLUSIONS: There is temporal interaction between BEV and the Notch signaling pathway, specifically with Notch4 and Delta-like-ligand-4 in PRPE cultures. This transient decrease in Notch signaling can impact the functionality of RPE cells. These findings can help to provide a better understanding of the effect of long-term usage of anti-VEGF agents in the treatment of retinal degenerative and vitreoretinopathy diseases.

Perivascular and Quadrant Nerve Fiber Layer Thickness and Its Relationship with Oxygen Saturation.

PURPOSE: To study whether there exists a relationship between retinal nerve fiber layer thickness and oxygen saturation and to identify whether perivascular thickness (pRNFL) or quadrant thickness (qRNFL) has a stronger correlation. METHODS: Patients without any detectable ocular abnormality on complete ophthalmic evaluation underwent non-invasive photo-spectrometric retinal oximetry on the Oxymap T1 retinal oximeter (Oxymap hf, Reykjavik, Iceland) and spectral-domain optical coherence tomography to determine if the pRNFL (Spectralis, Heidelberg, Germany) and the qRNFL (RtVue, Optovue) correlated with the measured light intensities and the calculated retinal oxygen saturations. RESULTS: 30 eyes of 30 patients (120 arterioles, 120 venules) were included in the study. The mean arteriolar saturations (%) were temporal: 84.5 (95% CI 82.7-86.3) and nasal: 93.5 (95% CI 91.0-95.8); venous saturations were temporal: 54.4 (95% CI 52.9-55.9) and nasal: 59.9 (95% CI 58.3-61.4). The mean pRNFL thickness (µm) around arterioles was temporal: 153.1 (95% CI 146-159) and nasal: 109.4 (95% CI 103-115); around venules it was temporal: 147.4 (95% CI 140-154) and nasal: 101.2 (95% CI 95-107). The oxygen saturations correlated significantly with pRNFL (arteriolar r = -0.514; p < 0.001 and venous r = -0.513; p < 0.001) but did not show a significant correlation with qRNFL values. CONCLUSION: This relationship between perivascular RNFL could be physiological or artifactual. If physiological, it would explain and form the basis of altered oxygen saturation in a multitude of diseases. If artifactual, it would necessitate the incorporation of a pRNFL correction. However, the results of this study enable us to expect increased saturation in areas of thinner RNFL or vice versa with the current methodology of retinal vessel oximetry as obtained by dual-wavelength photo-spectrometric fundus imaging.

Use of Wavefront Imaging Technology to Demonstrate Improvement in Corneal Aberrations Using Piggyback Contact Lens in a Keratoconus Eye With Intrastromal Corneal Ring Segment Implantation: A Case Report.

OBJECTIVE: To quantify short-term changes in corneal high-order aberrations (HOA) with piggyback contact lens use in an eye with keratoconus that had undergone intrastromal ring segment (Intacs) implantation. METHODS: A patient with keratoconus reporting of distorted images after Intacs surgery was found to have HOA (trefoil, point spread function [PSF], and modulation transfer function [MTF]) as measured using wavefront technology (Nidek OPD-Scan III) and evidenced by her cylindrical correction. She underwent piggyback contact lens (silicone hydrogel and fluoroperm rigid gas-permeable lenses) fitting in an attempt to improve the HOA. RESULTS: After piggyback contact lens fitting, her visual acuity improved and all her visual symptoms resolved. High-order aberrations reduced from 3.152 to 0.490 after the lens fitting and was noted to be 0.447 at 6 months; trefoil also significantly improved (0.360-0.096; it was 0.031 at 6 months). The cylinder decreased from -4.50 to -0.75 and was stable at 6 months (-1.00). There was also significant improvement in PSF and MTF. CONCLUSIONS: Visual acuity and symptoms along with HOA and cylinder improved after fitting of piggyback contact lens in our patient with keratoconus who had undergone Intacs.