Techniques and Preferences for Nonvalved Aqueous Shunts: A Survey of American Glaucoma Society Members.

PURPOSE: To assess practice patterns and opinions of glaucoma specialists regarding indications, surgical technique, and postoperative management for nonvalved aqueous shunts. DESIGN: Anonymous online survey study. PARTICIPANTS: American Glaucoma Society (AGS) members. METHODS: An anonymous online survey was distributed to glaucoma specialists via the AGS forum from June to August 2022. MAIN OUTCOME MEASURES: Survey questions and responses were assessed in 4 sections: (1) general demographics and practice patterns; (2) nonvalved tubes vs. trabeculectomy; (3) nonvalved tubes vs. valved tubes; and (4) nonvalved tube techniques. RESULTS: There were 132 respondents; nonvalved tubes were reported to be performed more often than trabeculectomy by 61% of respondents within 5 years of completing training and 23% of respondents with more than 15 years since completing training. The most frequently preferred types of nonvalved tubes were Baerveldt-350 (41%), Baerveldt-250 (27%), and ClearPath-250 (18%). In patients with lower target intraocular pressure (IOP), 92% of respondents preferred trabeculectomy over nonvalved tube; 33% cited a cutoff of < 12 mmHg, and 31% cited a cutoff of < 15 mmHg. In patients with higher preoperative IOP, 50% of respondents preferred valved over nonvalved tubes; 29% cited a cutoff of > 40 mmHg, and 38% cited a cutoff of > 30 mmHg. The most frequently used ligature was 7-0 Vicryl (69%). The most frequently used strategies for early IOP lowering were fenestrations without wicks (70%) and with wicks (22%), with one 10-0 Nylon being the most used wick technique (22%). Overall, 37% of respondents use a ripcord; among ripcord users, 55% use it for hypotony prevention (3-0 Prolene most common for this purpose at 35%), and 40% use it for optional early IOP lowering (4-0 Nylon most common for this purpose at 21%). If IOP is too high at postoperative week 4, 38% of respondents do not open the tube early. CONCLUSIONS: We demonstrate significant heterogeneity regarding specific indications, surgical technique, and postoperative management for nonvalved tubes. Future work is needed to identify and develop standardized guidelines alongside best practices. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.

Purpose: Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota. Methods: Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300 mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice. Results: Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV. Conclusions: These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.

The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.

Gut Microbiome and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, is strongly associated with gestational age and weight at birth. Yet, many extremely preterm infants never develop ROP or develop only mild ROP with spontaneous regression. In addition, a myriad of other factors play a role in the retinal pathology, one of which may include the early gut microbiome. The complications associated with early gestational age include dysbiosis of the dynamic neonatal gut microbiome, as evidenced by the development of often concomitant conditions, such as necrotizing enterocolitis. Given this, alongside growing evidence for a gut-retina axis, there is an increasing interest in how the early intestinal environment may play a role in the pathophysiology of ROP. Potential mechanisms include dysregulation of vascular endothelial growth factor and insulin-like growth factor 1. Furthermore, the gut microbiome may be impacted by other known risk factors for ROP, such as intermittent hypoxia and sepsis treated with antibiotics. This mini-review summarizes the literature supporting these proposed avenues, establishing a foundation to guide future studies.

Absence of Gut Microbiota Is Associated with RPE/Choroid Transcriptomic Changes Related to Age-Related Macular Degeneration Pathobiology and Decreased Choroidal Neovascularization.

Studies have begun to reveal significant connections between the gut microbiome and various retinal diseases, including age-related macular degeneration (AMD). As critical supporting tissues of the retina, the retinal pigment epithelium (RPE) and underlying choroid play a critical role in retinal homeostasis and degeneration. However, the relationship between the microbiome and RPE/choroid remains poorly understood, particularly in animal models of AMD. In order to better elucidate this role, we performed high-throughput RNA sequencing of RPE/choroid tissue in germ-free (GF) and specific pathogen-free (SPF) mice. Furthermore, utilizing a specialized laser-induced choroidal neovascularization (CNV) model that we developed, we compared CNV size and inflammatory response between GF and SPF mice. After correction of raw data, 660 differentially expressed genes (DEGs) were identified, including those involved in angiogenesis regulation, scavenger and cytokine receptor activity, and inflammatory response-all of which have been implicated in AMD pathogenesis. Among lasered mice, the GF group showed significantly decreased CNV lesion size and microglial infiltration around CNV compared to the SPF group. Together, these findings provide evidence for a potential gut-RPE/choroidal axis as well as a correlation with neovascular features of AMD.

Deep Learning for Hemorrhagic Lesion Detection and Segmentation on Brain CT Images.

Stroke is an acute cerebral vascular disease that is likely to cause long-term disabilities and death. Immediate emergency care with accurate diagnosis of computed tomographic (CT) images is crucial for dealing with a hemorrhagic stroke. However, due to the high variability of a stroke's location, contrast, and shape, it is challenging and time-consuming even for experienced radiologists to locate them. In this paper, we propose a U-net based deep learning framework to automatically detect and segment hemorrhage strokes in CT brain images. The input of the network is built by concatenating the flipped image with the original CT slice which introduces symmetry constraints of the brain images into the proposed model. This enhances the contrast between hemorrhagic area and normal brain tissue. Various Deep Learning topologies are compared by varying the layers, batch normalization, dilation rates, and pre-train models. This could increase the respective filed and preserves more information on lesion characteristics. Besides, the adversarial training is also adopted in the proposed network to improve the accuracy of the segmentation. The proposed model is trained and evaluated on two different datasets, which achieve the competitive performance with human experts with the highest location accuracy 0.9859 for detection, 0.8033 Dice score, and 0.6919 IoU for segmentation. The results demonstrate the effectiveness, robustness, and advantages of the proposed deep learning model in automatically hemorrhage lesion diagnosis, which make it possible to be a clinical decision support tool in stroke diagnosis.

Brainwide Genetic Sparse Cell Labeling to Illuminate the Morphology of Neurons and Glia with Cre-Dependent MORF Mice.

Cajal recognized that the elaborate shape of neurons is fundamental to their function in the brain. However, there are no simple and generalizable genetic methods to study neuronal or glial cell morphology in the mammalian brain. Here, we describe four mouse lines conferring Cre-dependent sparse cell labeling based on mononucleotide repeat frameshift (MORF) as a stochastic translational switch. Notably, the optimized MORF3 mice, with a membrane-bound multivalent immunoreporter, confer Cre-dependent sparse and bright labeling of thousands of neurons, astrocytes, or microglia in each brain, revealing their intricate morphologies. MORF3 mice are compatible with imaging in tissue-cleared thick brain sections and with immuno-EM. An analysis of 151 MORF3-labeled developing retinal horizontal cells reveals novel morphological cell clusters and axonal maturation patterns. Our study demonstrates a conceptually novel, simple, generalizable, and scalable mouse genetic solution to sparsely label and illuminate the morphology of genetically defined neurons and glia in the mammalian brain.

Choroidal Vessel Diameters in Pseudoexfoliation and Pseudoexfoliation Glaucoma Analyzed Using Spectral-Domain Optical Coherence Tomography.

PURPOSE OF THE STUDY: The purpose of the study was to analyze choroidal vessel diameters in pseudoexfoliation (PXF) and pseudoexfoliation glaucoma (PXFG) using spectral-domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Fifty patients (100 eyes) with PXF and PXFG who underwent high-definition 1-line raster SD-OCT imaging at New England Eye Center, Boston, were retrospectively identified and divided into unilateral PXFG (26 patients, 52 eyes), unilateral PXF (4 patients, 8 eyes), bilateral PXFG (4 patients, 8 eyes), and bilateral PXF (16 patients, 32 eyes). Eyes with concomitant chorioretinal pathology, history of shunting/filtering for glaucoma, and significant anisometropia were excluded. SD-OCT scans were divided into subfoveal, central, and peripheral zones and choroidal vessel diameters were measured. RESULTS: In patients with unilateral PXFG, mean choroidal vessel diameter was 12.9 µm smaller in the affected eyes when compared with their contralateral eyes (45.7 vs. 58.6 µm; P<0.0001) with the greatest reduction (16.6 µm) in the subfoveal zone (49.0 vs. 65.6 µm; P<0.0001). In patients with unilateral PXF, the mean choroidal vascular diameter was 13.3 µm smaller in the affected eyes when compared with their contralateral eyes (42.8 vs. 56.1 µm; P=0.02). As expected, no significant difference was observed between the 2 eyes of patients with bilateral PXFG (45.5 vs. 45.7 µm; P=0.95) and bilateral PXF (51.4 vs. 50.2 µm; P=0.52). CONCLUSIONS: Choroidal vessel diameters are smaller in the affected eyes of patients with unilateral PXF and PXFG when compared with their contralateral unaffected eyes. These changes appear to be independent of the presence or absence of glaucoma. Future studies may identify the choroidal vascular changes and their relationship with the pathogenesis of these conditions.

Reproducibility of a long-range swept-source optical coherence tomography ocular biometry system and comparison with clinical biometers.

OBJECTIVE: To demonstrate a novel swept source optical coherence tomography (SS-OCT) imaging device using a vertical cavity surface-emitting laser (VCSEL) capable of imaging the full eye length and to introduce a method using this device for noncontact ocular biometry. To compare the measurements of intraocular distances using this SS-OCT instrument with commercially available optical and ultrasound biometers. To evaluate the intersession reproducibility of measurements of intraocular distances using SS-OCT. DESIGN: Evaluation of technology. PARTICIPANTS: Twenty eyes of 10 healthy subjects imaged at the New England Eye Center at Tufts Medical Center and Massachusetts Institute of Technology between May and September 2012. METHODS: Averaged central depth profiles were extracted from volumetric SS-OCT datasets. The intraocular distances, such as central corneal thickness (CCT), aqueous depth (AD), anterior chamber depth (ACD), crystalline lens thickness (LT), vitreous depth (VD), and axial length (AL), were measured and compared with a partial coherence interferometry device (IOLMaster; Carl Zeiss Meditec, Inc., Dublin, CA) and an immersion ultrasound (IUS) A-scan biometer (Axis-II PR; Quantel Medical, Inc., Cournon d'Auvergne Cedex, France). MAIN OUTCOME MEASURES: Reproducibility of the measurements of intraocular distances, correlation coefficients, and intraclass correlation coefficients. RESULTS: The standard deviations of the repeated measurements of intraocular distances using SS-OCT were 6 µm (CCT), 16 µm (ACD), 14 µm (AD), 13 µm (LT), 14 µm (VD), and 16 µm (AL). Strong correlations among all 3 biometric instruments were found for AL (r > 0.98). The AL measurement using SS-OCT correlates better with the IOLMaster (r=0.998) than with IUS (r=0.984). The SS-OCT and IOLMaster measured higher AL values than ultrasound (175 and 139 µm, respectively). No statistically significant difference in ACD between the optical (SS-OCT or IOLMaster) and ultrasound methods was detected. High intersession reproducibility of SS-OCT measurements of all intraocular distances was observed with intraclass correlation coefficients >0.99. CONCLUSIONS: The SS-OCT using VCSEL technology enables full eye length imaging and high-precision, noncontact ocular biometry. The measurements with the prototype SS-OCT instrument correlate well with commercial biometers. The SS-OCT biometry has the potential to provide clinically useful comprehensive biometric parameters for pre- and postoperative eye evaluation.

Analysis of the morphology and vascular layers of the choroid in retinitis pigmentosa using spectral-domain OCT.

BACKGROUND AND OBJECTIVE: To analyze choroidal morphology and vascular layers in eyes with retinitis pigmentosa (RP) using spectral-domain optical coherence tomography. PATIENTS AND METHODS: Cross-sectional, retrospective analysis of 14 patients (14 eyes) with RP and 33 healthy subjects (33 eyes) who underwent high-definition one-line raster scanning at a single center. Two independent raters evaluated the morphology, thickness, and vascular layers of the choroid in both groups. RESULTS: The choroid had an irregular shape in 11 of 14 eyes (79%) with RP. The thickest point of choroid was not subfoveal as in healthy eyes, and exaggerated nasal thinning of the choroid was observed in nine of 14 eyes (65%) with RP. Mean subfoveal total choroidal thickness and large choroidal vessel layer thickness were significantly lower in eyes with RP (P = .04 and P = .02, respectively) than in healthy eyes. CONCLUSION: Choroidal morphology is altered and an exaggerated thinning of the large choroidal vessel layer is observed in eyes with RP. Further studies involving correlation of disease stage and severity with choroidal changes may provide further insight into the involvement of choroid in RP and other inherited retinal dystrophies.

Retinal neovascularization secondary to proliferative diabetic retinopathy characterized by spectral domain optical coherence tomography.

PURPOSE: The purpose of this study was to characterize diabetic retinal neovascularization (NV) and accompanying retinal and vitreal morphologic changes using high-resolution spectral domain optical coherence tomography. METHODS: A cross-sectional retrospective analysis was performed on 16 eyes of 14 nonconsecutive subjects with proliferative diabetic retinopathy that were seen between August 2011 and December 2011 at the New England Eye Center, Boston, MA. Patients who had NV of the disk, NV elsewhere, and intraretinal microvascular abnormalities were scanned using optical coherence tomography directly over the region of the abnormal vessels. RESULTS: Characteristic changes of the retinal vasculature, retina, and vitreous were seen in the 16 eyes with NV. This study describes optical coherence tomography characteristics of 1) NV of the disk, 2) NV elsewhere, 3) intraretinal microvascular abnormality, 4) NV causing traction without retinal detachment; and 5) NV causing traction with retinal detachment. The morphologic appearance of vitreous traction was found to be consistent with the previous histologic reports. CONCLUSION: It is possible to image diabetic NV using spectral domain optical coherence tomography and to visualize the spectrum of retinal, retinal vascular, and vitreal changes seen through these areas of abnormal retinal vasculature.

Exercise-induced acute changes in systolic blood pressure do not alter choroidal thickness as measured by a portable spectral-domain optical coherence tomography device.

PURPOSE: To measure choroidal thickness in patients manifesting an acute change in systemic arterial blood pressure using a portable spectral-domain optical coherence tomography device (iVue). METHODS: Fifteen patients (15 eyes) undergoing cardiac exercise stress testing were scanned using a portable spectral-domain optical coherence tomography system (iVue). Two scan protocols were used: cross line scan for measuring choroidal thickness and the retina map scan to measure retinal thickness. Each patient was scanned before and within 3 minutes after the stress test. Blood pressure was measured at the same time as the acquisition of the scans. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid-sclera junction at 500-µm intervals up to 1,000 µm temporal and nasal to the fovea. Retinal thickness was measured by an automated software. All choroidal thickness measurements were performed by two independent observers. RESULTS: Fifteen patients (15 eyes) with a mean age of 60.6 (±10.4 years) were scanned. There was a significant increase in systolic but not diastolic pressure after stress testing (P < 0.05). The mean choroidal thickness measurements showed no significant difference before and after exercise stress testing (P > 0.05). In addition, there was no significant difference in retinal thickness before and after stress testing measurements (P > 0.05). CONCLUSION: There was no change in choroidal thickness or retinal thickness, despite an acute change in the systemic systolic blood pressure induced by exercise.

A case-controlled matched-pair cohort study of single-incision and conventional laparoscopic gastric band patients in a single US center with 1-year follow-up.

INTRODUCTION: Single-incision laparoscopic gastric banding has been reported to be safe and feasible. This matched case-control study is the first to compare the outcome in terms of weight loss and comorbidity improvement and band positioning of single-incision versus conventional laparoscopic gastric banding with 1-year follow-up. PATIENTS AND METHODS: Patients undergoing gastric banding surgery by one surgeon (S.V.) were prospectively entered into a database. Data collected included basic demographics, perioperative parameters, early and late postoperative (PO) morbidity, weight loss, and phi angle. Ten patients who underwent a single-incision gastric banding procedure were matched one-to-two with 20 patients undergoing conventional gastric banding from a database of 151 patients. Match was obtained according to gender, body mass index (BMI) ± 4 kg/m(2), age ± 8 years, and presence of at least one comorbidity in common. Generalized linear mixed models were used for statistical analysis. RESULTS: Patients' initial characteristics were similar: SIL and conventional, respectively: sex (female:male) 9:10 and 18:20; age (years): 36.5 ± 10 and 37.5 ± 9; preoperative BMI (kg/m(2)): 41.8 ± 4 and 42.4 ± 3; weight (kg): 110.2 ± 13 and 117.9 ± 13; hospital stay (days): 1 and 1; operative time (min): 106.6 ± 24 and 100.9 ± 22. No significant differences were found in patients' BMI or excess weight loss during 1-year follow-up. The phi angles of the bands varied in a comparable range: PO day 1 (degrees): 62 ± 13 and 59 ± 15; PO week 6: 55 ± 9 and 54 ± 11, for SIL and conventional, respectively. CONCLUSIONS: In this matched case-controlled study, single-incision laparoscopic adjustable gastric banding surgery outcomes were similar to those of the conventional multi-trocar laparoscopic operation. Band position as described by phi angle was also similar in the two groups. These results suggest that use of a single-incision approach does not compromise the results or band positioning of gastric banding surgery.