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Purpose: Determine rates of progression of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) to complete retinal pigment epithelium and outer retinal atrophy (cRORA) and rates of progression of drusen to iRORA/cRORA in eyes with geographic atrophy (GA) treated with avacincaptad pegol (ACP)., Methods: Post hoc analysis of the GATHER1 prospective, randomized, double-masked Phase II/III study that evaluated ACP 2 mg vs. sham. Optical coherence tomography (OCT) data from GATHER1 were transferred to the Doheny Image Reading and Research Lab for masked analysis by readers experienced with Classification of Atrophy Meeting (CAM) grading features. Regions of OCT volume scans more than 500 µm from the border of GA lesions were evaluated at baseline and at months 6, 12, and 18. Participants with iRORA and/or drusen (≥ 40 µm height on OCT) at baseline were included in the analysis., Results: The proportion of eyes progressing from iRORA to cRORA in the ACP 2 mg group was 5.0%, 15.0%, and 20.0% at months 6, 12, and 18 respectively, as compared with 11.8%, 30.2%, and 41.8% of eyes in the sham group. The proportion of ACP 2 mg-treated eyes progressing from drusen to iRORA or cRORA was 3.8%, 7.6%, and 7.6% at months 6, 12, and 18 compared with 15.9%, 18.1%, and 27.2% of sham-treated eyes., Conclusions: Rates of progression from iRORA to cRORA and drusen to iRORA/cRORA were reduced in eyes treated with ACP 2 mg vs. sham, with increasing separation between groups over time, suggesting early intervention may slow disease progression., Trial Registration: ClinicalTrials.gov identifier: NCT02686658. Date of registration: February 16, 2016., Key Messages: What is known Geographic atrophy is an advanced form of age-related macular degeneration (AMD) that leads to irreversible vision loss, presenting a significant public health unmet need. The Classification of Atrophy Meeting (CAM) group recommended a new nomenclature for advanced AMD lesions, based on the affected anatomical layers on optical coherence tomography. Accordingly, the terms incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) were introduced (Guymer et al., Ophthalmology 127:394-409, 2020; Sadda et al., Ophthalmology 125:537-548, 2018). What is new GATHER1 post hoc analysis shows that treatment with avacincaptad pegol (ACP) 2 mg decreases the proportion of eyes that progress from iRORA to cRORA, and from drusen to iRORA or cRORA, compared with sham, over 6, 12, and 18 months. These findings suggest a potential role for ACP in delaying the progression of existing pre-atrophic AMD lesions., Competing Interests: Declarations Ethics approval The GATHER1 trial was performed in accordance with the tenets of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines [13]. The appropriate ethics committee or institutional review board at each study center involved in the study (80 centers) approved the protocol [13]. Consent to participate Written informed consent was obtained from all participants [13]. Disclosure statement SriniVas R Sadda- although the author is the editor of the journal, there was no involvement with the peer review process for this article. Competing interests GC has received lecture fees from Nidek. AK, SS, SL, SBV, FC, YA, and MGN have no financial disclosures. SR Sadda has consulted/advised for: Apellis Pharmaceuticals, Inc.; Amgen Inc.; AbbVie/Allergan, Inc.; Samsung Bioepis; Biogen; Boehringer Ingelheim; Iveric Bio; Novartis; Roche/Genentech; Bayer Healthcare Pharmaceuticals; Regeneron Pharmaceuticals, Inc.; Pfizer Inc.; Astellas; Nanoscope Therapeutics; Janssen Pharmaceuticals, Inc.; CenterVue, Inc.; Optos, Inc.; and Heidelberg Engineering; has received lecture fees/speakers bureau fees from: Heidelberg Engineering; Roche/Genentech; Novartis; and Optos, Inc.; and has received research equipment from: CenterVue, Inc.; Optos, Inc.; Carl Zeiss Meditec; Topcon Medical Systems, Inc.; Heidelberg Engineering; and Nidek Inc. SR Sadda, the corresponding author, is an editor of the journal; however, there was no involvement with the peer review process for this article. DD and LZ are former employees of Astellas, and DA is an employee of Astellas., (© 2024. The Author(s).)

Purpose: Compare choroidal changes in ranibizumab versus panretinal photocoagulation (PRP)-treated eyes with proliferative diabetic retinopathy (PDR)., Methods: DRCR Retina Network Protocol S post hoc analysis evaluated optical coherence tomography change in choroidal thickness (subfoveal and 3mm superior and inferior to the fovea) through five years; choroidal vascularity index (CVI) was assessed at baseline and one year. Mixed linear models for choroidal change included adjustments for the baseline choroidal value and age., Results: This study included 328 eyes (158 ranibizumab and 170 PRP) from 256 participants (88 ranibizumab and 95 PRP eyes at five years). Mean change in choroidal thickness from baseline to five years at the fovea was -12 µm in ranibizumab versus -8 µm in PRP (difference [95% confidence interval]: -4 [-18 to 10], P = 0.57), superior was -14 µm versus -19 µm (difference: 5 [-8 to 17], P = 0.45) and inferior was -26 µm versus -32 µm [difference: 5 (-9 to 20), P = 0.45]; change at all three points within the ranibizumab group, and the superior and inferior points for PRP, were statistically significant (P < .05). Mean change in CVI at one year was -0.02% in ranibizumab versus -0.95% in PRP (difference: 0.93 [-0.35 to 2.21], P = 0.14)., Conclusions: In patients with PDR, treatment with ranibizumab versus PRP did not result in statistically significant differences in five-year choroidal thickness or one-year CVI change. Both groups had significant decreases in choroidal thickness at five years., Translational Relevance: Ranibizumab treatment for PDR did not statistically significantly affect choroidal thickness or vascularity differently than PRP.

Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable., Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD., Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023., Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years., Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase., Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 μm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants)., Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

Background: Polycyclic aromatic hydrocarbons (PAHs) constitute a group of chemicals with an omnipresence in the environment and our surroundings. With their genotoxicity and carcinogenic nature, it has been proven to be monstrous in our daily life and, especially for pregnant women and their newborn., Aim: This questionnaire study was done to verify the influence of domestic exposure to polyaromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring in the suburban and the rural population of Mysore., Methodology: Two hundred pregnant women as patients from four different hospitals in Mysore were given a questionnaire to be filled with 24 parameters ranging from the knowledge to various means of exposure to the pregnant women with the PAH and the severity and the extent of the orofacial defect in the newborn., Results: It was determined that exposure of pregnant women to the smoke emanating from the method of cooking or heating to smoking (first or passive) and the direct inhalation of gas had the maximum effects on the association of cleft palate (60.7%) in unilateral followed by 90.9% in bilateral, 65.0% in soft tissue, and 76.2% in hard tissue cleft palate., Conclusion: The deleterious effects of the cooking and water heating measures practiced in the suburban and the rural population predisposed the pregnant women to significantly higher chances of offspring with the varied extent of the orofacial defect. There is an influence of domestic exposure to polycyclic aromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Background: Peri-implantitis can be attributed to many underlying causes, one of the chief ones being due to infection caused by oral micro flora and particularly Aggregatibacter actinomycetemcomitans . Antibiotics are administered along with mechanical debridement to control the infection. The side effect of conventional antibiotic therapy and drug resistance has led to the necessity for alternate approaches to handle infections. Natural products are being investigated because of their multi-target activity and structurally different from the normal antibiotics. Propolis a product by Apis Mellifera bees as a wound healing and bone regenerating effect along with antimicrobial effect. One of the important features of Propolis is the chemical properties of Propolis changes with the different locations of procurement. Antimicrobial activity of Hubballi propolis against Aggregatibacter actinomycetemcomitans is not been reported in the literature., Aim: The aim of this study is to evaluate the antimicrobial effect of the Hubballi Propolis against Aggregatibacter actinomycetemcomitans ., Methods: The two solvents used for the study were water and 70% Aq ethanol. Minimum inhibitory concentration (MIC), total phenolic contents (TPC), and total flavonoid content (TFC) were tested., Results: Hubballi Propolis sample showed antimicrobial effect against Aggregatibacter actinomycetemcomitans with MIC range from 0.1 mg/ml to 0.25 mg/ml., Conclusion: Hubballi Propolis is effective against Aggregatibacter actinomycetemcomitans infection thus may help in treating peri-implantitis. Propolis extracted with water as solvent showed better MIC, higher TPC and TFC than the propolis extracted using alcohol as solvent. This feature is noteworthy as the formulations produced using water extract is favorable than alcohol extract of propolis which irritates the mucosa and hence difficult for its application in dentistry., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Aim: To systematically evaluate the literature evidence regarding the suitability of the T-scan occlusal system for implant supported prostheses., Materials and Methods: A thorough bibliographic search was conducted on PubMed, Google Scholar, Cochrane library, Web of Science, EMBASE, and Scopus to collect relevant articles published from January 1, 2008 to August 30, 2021, using a combination of the following words:
"T-scan," "Implant supported prostheses," and "dental implant" according to the PRISMA guidelines for the focused research question constructed using the PICO criteria. Randomized control trials, prospective studies, retrospective studies on the use of T-scan system in implant-supported prostheses reported in English language were included in the study., Results: This review consisted of 17 studies and 359 patients rehabilitated with 1,126 implants. In 3 studies, removable types of prostheses were given over implants, and in 14 studies, fixed types of prostheses were given. Nine studies determined the percentage of occlusal force magnitude and occlusion time sequence. Three studies measured the localization of the occlusion center. T-scan was used in two studies to measure the amount of gingival crevicular fluid after occlusal adjustment. The follow-up period ranged from 6 months to 2 years or more., Conclusion: T-scan proved with better results than other occlusal analysis indicators in terms of occlusion measurement, clinical execution, quantify the location and contact timing, and occlusion in 3D with more precision., Clinical Significance: T-scan occlusal analysis system is widely used in dentistry and there is an increase in the number of studies, so a systematic review evaluating and comparing results is warranted.

Background: Although an optical coherence tomography (OCT)-derived central drusen volume ≥0.03 mm 3 has been found to be a risk factor for progression to late age-related macular degeneration (AMD), this parameter is not currently available on most OCT devices or acquisition protocols. The purpose of this study was to evaluate the ability of human graders to qualitatively assess drusen volume by inspection of OCT B-scans., Methods: 100 subjects (200 eyes) from the Amish Eye Study diagnosed with early or intermediate AMD underwent OCT imaging with both Cirrus OCT and Spectralis OCT. Drusen volume was automatically computed from the Cirrus OCT volumes using the Cirrus Advanced RPE Analysis software. Spectralis volume scans were reviewed by two independent, masked graders who were asked to determine whether the central drusen volume was ≥0.03 mm 3 . Cohen's kappa coefficients were computed to assess the agreement., Results: After excluding 11 eyes with poor image quality and 5 eyes used for training of the graders, the remaining 184 eyes were included in this analysis. The agreement between the graders and the automated evaluation of drusen volume by the Cirrus OCT was excellent with K = 0.88 for grader 1 and K = 0.82 for grader 2. The agreement between graders was also excellent with a K = 0.88., Conclusions: The presence of a high central drusen volume can be assessed reliably by qualitative inspection of OCT B-scans. This approach may be useful in the assessment of risk for progression to late AMD., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Propolis, a natural antibiotic, which is in high demand in dentistry is a resinous substance. The main ingredient of propolis that is required for antibiotic effect is flavonoids and phenolic acids. Although propolis is a promising option for the control of oral microbes with lower related hazards and a good immunomodulator effect, its composition differs considerably depending on its botanical origin, the site and the season of collection. This original research aims to find the chemical composition and minimum inhibitory concentration (MIC) of propolis procured from different places of Karnataka state. The results would help the dentist and the pharmacist to select the best propolis to use as antibiotics in treating oral disease., Materials and Methods: Propolis sample from 5 different locations of Karnataka was procured from single apiary in Bangalore. Extraction of propolis using two different extracting solvents was carried out. The total phenolic content, total flavonoid content and MIC of each sample were analyzed., Results: Water extract propolis of Sullia and Hubli was highly active against tested organism with the MIC <0.312; alcohol extract of Sullia, Hubli and Chitradurga was moderately active with the MIC between 0.312 and 5 mg/ml. Vijayapura and Bagalkot were least active with the MIC >5 mg/ml at tested concentration., Conclusion: Propolis procured from different locations of Karnataka can be used as an antimicrobial agent with varying concentrations. However, when propolis is procured for therapeutic purpose, then it needs to be tested for its chemical composition before being utilized., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Oral and Maxillofacial Pathology.)

Purpose: To study the effect of monthly 0.3-mg intravitreal ranibizumab injections on intraretinal hard exudates (HEs) and correlate the effect with macular thickness in eyes with diabetic macular edema (DME)., Design: Randomized, controlled trial., Methods: Twenty-four eyes of 24 subjects with DME were included in this institutional review board-approved, prospective longitudinal study. Subjects were randomly assigned to receive monthly intravitreal ranibizumab injections either until macular edema resolved or until both macular edema and HEs resolved. All subjects underwent spectral-domain optical coherence tomography imaging (Cirrus OCT), at baseline and monthly for 12 months. Mean HE area and mean macular thickness at baseline and month 12 were compared using a paired t test and correlated with Pearson analysis., Results: The average age of the 24 subjects was 65 (±8.55) years. There was a significant decrease (P = .001) in mean HE area from baseline (0.48 ± 0.43 mm 2 ) to month 12 (0.17 ± 0.19 mm 2 ). There was a significant increase (P < .001) in best-corrected visual acuity from a letter score of 63.38 (±7.92) at baseline to 76.38 (±8.93) at month 12. There was no additional vision benefit for continuing to treat with monthly injections for persistent HE in the absence of macular thickening., Conclusion: In eyes with DME, monthly intravitreal ranibizumab injections resulted in significant reduction in intraretinal HEs that paralleled reductions in macular thickness and volume. Baseline foveal HEs were associated with worse vision outcomes, and continued treatment for persistent HEs in the absence of edema did not result in better vision., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To evaluate the reproducibility of intraretinal hard exudate (HE) quantification from spectral domain optical coherence tomography (SD-OCT) images of eyes with diabetic retinopathy (DR)., Methods: Cases with diabetic macular edema were enrolled. The area of HE obtained by B-scan segmentation was compared with the area obtained by en face segmentation., Results: The mean ± SD for the HE area was 1.78 ± 1.37 mm with B-scan segmentation and 0.72 ± 0.82 mm with the automated en face analysis tool; the absolute difference was 1.01 ± 0.64 mm. There was excellent correlation in total HE area between the two methods (r = 0.95, P < 0.0001). The HE volume was 0.06 ± 0.07 mm. The correlation between HE volume and en face HE area was high (r = 0.95, P < 0.001). Intergrader reproducibility yielded excellent agreement with an intraclass correlation coefficient value of 0.99 (95% CI 0.994-0.999) for the en face approach and 0.99 (95% CI 0.977-0.997) for manual segmentation., Conclusion: Quantification of HE in eyes with diabetic retinopathy can be performed reliably using en face segmentation and, though the en face results are consistently lower, correlates well with HE measurements obtained by exhaustive segmentation of all B-scans in dense volume optical coherence tomography (OCT).

Purpose: To evaluate retinal blood flow measurements in normal eyes and eyes with varying levels of diabetic retinopathy (DR) using Doppler Fourier-domain optical coherence tomography (FD-OCT)., Methods: Twenty-two eyes of 19 subjects, 10 with severe nonproliferative DR (NPDR) and 12 with proliferative DR (PDR), were compared with 44 eyes of 40 healthy control subjects. All eyes were scanned by RTvue FD-OCT. Color disk photographs and cube/volume scans of the optic nerve head were obtained. Doppler OCT scans and accessory imaging data were imported into Doppler OCT of Retinal Circulation grading software to calculate TRBF and vascular parameters (e.g., venous and arterial cross-sectional area). Measurements were compared between cases and controls using independent t-tests., Results: Mean TRBF was 44.98 ± 9.80 (range: 30.18-64.58) µL/minute for normal eyes, 35.80 ± 10.48 (range: 20.69-49.56) µL/minute for eyes with severe NPDR, and 34.79 ± 10.61 (range: 16.77-48.9) µL/minute for eyes with PDR. Mean TRBF was significantly lower in eyes with severe NPDR (P = 0.01) and PDR (P = 0.003) than in normal eyes., Conclusion: Total retinal blood flow was significantly lower in eyes with severe NPDR and PDR compared with normal eyes. Retinal blood flow determined by Doppler OCT may be a useful parameter for evaluating patients with DR.

Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography.

Objective: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders., Design: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS., Participants: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013., Methods: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration., Main Outcome Measures: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome., Results: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective., Conclusions: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Purpose: To compare the lamina cribrosa (LC) intensity in glaucoma-suspect eyes and eyes with mild to moderate glaucoma using swept-source optical coherence tomography., Methods: Optic disc volume scans were collected using swept-source optical coherence tomography in 19 clinically defined glaucoma-suspect eyes and 29 eyes with mild to moderate glaucoma. LC intensity was measured using Image J software, and the resultant values were normalized using the retinal pigment epithelium and vitreous signal., Results: Mean age was 53.7±18.5 years in the glaucoma-suspect eyes and 63.0±16.1 years in the eyes with mild to moderate glaucoma (P=0.161). Significant differences in LC intensity were observed between the 2 groups, with median LC intensity values of 0.96 and 0.86 units in the glaucoma-suspect and the mild to moderate glaucoma groups, respectively (P<0.001). A weak positive correlation was found between mean deviation and normalized LC intensity (r=0.344; P=0.018)., Conclusions: Intensity measurement of the LC is a potential novel parameter which warrants further study in the setting of glaucoma.

Purpose: We characterized the foveal avascular zone (FAZ) and the parafoveal capillary network in healthy subjects using swept source OCT optical microangiography (OMAG)., Methods: We acquired OMAG images of the macula of 19 eyes (13 healthy individuals) using a prototype swept source laser OCT. En face images of the retinal vasculature were generated for superficial and deep inner retinal layers (SRL/DRL) in regions of interest 250 (ROI-250) and 500 (ROI-500) μm from the FAZ border., Results: The mean area (mm2) of the FAZ was 0.304 ± 0.132 for the SRL and 0.486 ± 0.162 for the DRL (P < 0.001). Mean vessel density (%) was 67.3 ± 6.4 for the SRL and 34.5 ± 8.6 for the DRL in the ROI-250 (P < 0.001), and 74.2 ± 3.9 for the SRL and 72.3 ± 4.9 for the DRL in the ROI-500 (P = 0.160)., Conclusions: Swept source OMAG images of healthy subjects allowed analysis of the FAZ and the density of the parafoveal capillary network at different retinal layers.

Purpose: To evaluate the feasibility and clinical utility of a novel noncontact scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiographic system., Methods: Ultra-widefield indocyanine green angiographic images were captured using a modified Optos P200Tx that produced high-resolution images of the choroidal vasculature with up to a 200° field. Ultra-widefield indocyanine green angiography was performed on patients with a variety of retinal conditions to assess utility of this imaging technique for diagnostic purposes and disease treatment monitoring., Results: Ultra-widefield indocyanine green angiography was performed on 138 eyes of 69 patients. Mean age was 58 ± 16.9 years (range, 24-85 years). The most common ocular pathologies imaged included central serous chorioretinopathy (24 eyes), uveitis (various subtypes, 16 eyes), age-related macular degeneration (12 eyes), and polypoidal choroidal vasculopathy (4 eyes). In all eyes evaluated with ultra-widefield indocyanine green angiography, high-resolution images of choroidal and retinal circulation were obtained with sufficient detail out to 200° of the fundus., Conclusion: In this series of 138 eyes, scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiography was clinically practical and provided detailed images of both the central and peripheral choroidal circulation. Future studies are needed to refine the clinical value of this imaging modality and the significance of peripheral choroidal vascular changes in the diagnosis, monitoring, and treatment of ocular diseases.

Purpose: To measure total retinal blood flow (TRBF) in normal, healthy Chinese Americans by using semi-automated analysis of Doppler Fourier-domain optical coherence tomography (FD-OCT) scans., Methods: Two hundred sixty-six normal, healthy Chinese-American participants (266 eyes) were enrolled from The Chinese American Eye Study. All participants underwent complete ophthalmic examination, including best-corrected visual acuity, indirect ophthalmoscopy, and Doppler FD-OCT imaging, using the circumpapillary double circular scan protocol. Total retinal blood flow and other vascular parameters (e.g., venous and arterial cross-sectional area and their velocities) were calculated by using Doppler OCT of Retinal Circulation software. Associations between TRBF and other clinical parameters were assessed by using bivariate correlations and linear regression., Results: The mean age of study participants was 57.40 ± 5.60 (range, 50-82) years. The mean TRBF was 49.34 ± 10.08 (range, 27.17-78.08, 95% confidence interval: 25.98-69.10) μL/min. The mean venous area was 0.0548 (±0.0084) mm(2). Superior retinal hemispheric blood flow (25.50 ± 6.62 μL/min) was slightly greater than inferior retinal hemispheric blood flow (23.84 ± 7.19 μL/min, P = 0.008). The mean flow velocity was 15.16 ± 3.12 mm/s. There was a weak but significant negative correlation between TRBF and age (r = -0.15, P = 0.012). No significant correlation was found between TRBF and axial length (r = 0.11, P = 0.08). Retinal blood flow was not significantly correlated with any other clinical parameters, including body mass index, systolic blood pressure, diastolic blood pressure, and intraocular pressure., Conclusions: Normal Doppler OCT-derived total retinal blood values in a Chinese-American population showed considerable variability, some of which was explained by age. These observations should help design future studies evaluating TRBF in populations with eye disease., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere., Design: Prospective, nonrandomized, case-control study., Participants: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls., Methods: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed., Main Outcome Measures: Total and hemispheric RS, RBF, RNFL, and GCC values., Results: The total RBF (34.6±12.2 μl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 μl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 μl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 μm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 μm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 μl/minute), RNFL (103.7 ± 20.6 μm), and GCC (83.6 ± 10.1 μm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 μl/minute, 124.8 ± 9.6 μm, and 96.1 ± 5.7 μm, respectively)., Conclusions: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of panretinal photocoagulation (PRP) on retinal blood flow and shear rate using Doppler Fourier-domain optical coherence tomography (FD-OCT) in poorly controlled diabetics with proliferative diabetic retinopathy (PDR)., Methods: This was a prospective interventional pilot study in patients with a new clinical diagnosis of PDR. Retinal blood flow and vessel diameter were measured using Doppler FD-OCT according to a previously described method, immediately before PRP treatment and 7 to 8 weeks after the last PRP session., Results: Ten patients with poorly controlled PDR (mean hemoglobin A1C = 9.2 ± 2.0%) and 10 control subjects were included in the study. PDR patients had significantly lower blood flow (∼25%) than control subjects both at baseline (P = 0.01) and after PRP (P = 0.003). Compared to controls, venous and arterial velocities were significantly decreased in diabetics at baseline (∼27%; P < 0.001 and 0.017, respectively) as well as after PRP (P < 0.001 and 0.006, respectively). Compared to controls, venous and arterial shear rates were significantly reduced in diabetics at baseline (∼27%; P = 0.002, 0.03) and after PRP (P = 0.002, 0.03). PRP in this group of PDR patients did not have a statistically significant effect on retinal blood flow or vessel parameters, though there was a trend for decreased arterial diameter (P = 0.09)., Conclusions: This is the first study to use Doppler FD-OCT to quantify functional changes in retinal vascular parameters in poorly controlled PDR patients. Compared to controls, blood flow parameters in these patients were decreased at baseline, but did not decrease further following PRP, with important implications related to diabetes control, endothelial function, and therapeutic response.

Background: Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis., Methods: The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects., Results: The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness., Conclusions: Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.

Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/-) mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of CCR5 in human T cells results in enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2 protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation. Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5 had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5 expression also promoted IL-2-dependent events, including CD25 expression, STAT5 phosphorylation, and T cell proliferation. We therefore suggest that by influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2-dependent events, CCR5 may play a critical role in T cell responses. In accord with our prior inferences from genetic-epidemiologic studies, such CCR5-dependent responses might constitute a viral entry-independent mechanism by which CCR5 may influence HIV-AIDS pathogenesis.