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1.
J Vitreoretin Dis ; 8(3): 286-292, 2024.
Article in English | MEDLINE | ID: mdl-38770068

ABSTRACT

Purpose: To quantify the Medicare reimbursement disparity between female and male vitreoretinal surgeons. Methods: Reimbursement reports were obtained from the US Center for Medicare and Medicaid Services from 2013 through 2020, which detail all Medicare Part B services. A vitreoretinal surgeon was defined as any provider with at least 10 charges of a Healthcare Common Procedure Coding System code related to vitrectomy or retinal detachment repair. Providers were grouped by sex, and the average total reimbursement rate and additional secondary statistics to quantify the reimbursement disparity were identified. Results: On average, female vitreoretinal surgeons were reimbursed 65% that of their male counterparts in 2020, $1.66 million to $2.56 million. The percentage of the average male vitreoretinal specialist's total reimbursement that the average female vitreoretinal specialist received decreased 8.8% from 2013 to 2020, from 73.8% to 65.0%. Conclusions: The reimbursement that the average female vitreoretinal surgeon receives from Medicare is only two thirds that of the average male vitreoretinal surgeon. In addition, there was no identifiable improvement in this disparity over the study period. Further efforts must be taken to establish concerted efforts to improve the reimbursement disparity and to identify the systematic inequities that led to its presence in the first place.

2.
Int J Med Inform ; 185: 105411, 2024 May.
Article in English | MEDLINE | ID: mdl-38492409

ABSTRACT

PURPOSE: This study aims to assess the extent to which the demand for ophthalmologic care among patients at the state level is reflected in Google Trends data, serving as an indicator of patient desire in ophthalmology. METHODS: For each state, patient interest in ophthalmologic care was estimated using the Google Trends resource measuring web search and YouTube search rates for multiple ophthalmologic terms. We compared the change in search for ophthalmologic terms over time and used ordinary least squares regression to evaluate whether search interest for ophthalmologic terms was able to predict the rate of practicing ophthalmologists in each state. We also compare the changing rates of searches across the web and YouTube to evaluate the resources patients are most likely to utilize. RESULTS: From 2008 to 2022, web search rates for general ophthalmology related terms increased by 43.98%, while search interest for retinal specific terms increased by 19.51%. YouTube specific results for general ophthalmology terms increased by 55.83% while search for retinal terms fell by 58.48%. Ophthalmologic and retinal specific search interest was not significantly associated with either outcome. CONCLUSIONS: Our findings suggest that patient information needs, demographic elements, and the educational backgrounds of residents and fellows - those important factors - are surprisingly poorly correlated with ophthalmology provider density. Furthermore, we observed no noteworthy correlation between the search interest in ophthalmology and the overall density of ophthalmologists or retinal specialists. This implies that there is a pressing need to explore and implement strategies aimed at better aligning these influencing factors the choices made by ophthalmologists in selecting their practice locations to bridge the gap between healthcare availability and public interest.


Subject(s)
Ophthalmology , Humans , Health Facilities
3.
Transl Vis Sci Technol ; 11(9): 7, 2022 09 01.
Article in English | MEDLINE | ID: mdl-36107113

ABSTRACT

Purpose: The purpose of this study was to evaluate the impact of image processing on quantitative metrics in optical coherence tomography angiography (OCTA) images and study conclusions in patients with diabetes. Methods: This was a single center, retrospective cross-sectional study. OCTA imaging with the Cirrus HD-OCT 5000 AngioPlex of patients with diabetes was performed. The 8 × 8 mm superficial slab images underwent 4 different preprocessing methods (none, background subtraction [BGS], foveal avascular zone brightness adjustment, and contrast limited adaptive histogram equalization [CLAHE]) followed by 4 different binarization algorithms (global Huang, global Otsu, local Niblack, and local Phansalkar) in ImageJ. Vessel density (VD), skeletonized VD (SVD), and fractal dimension (FD) were calculated. Mixed-effect multivariate linear regressions were performed. Results: Two hundred eleven scans from 104 patients were included. Of these scans, 67 (31.8%) had no diabetic retinopathy (DR), 99 (46.9%) had nonproliferative DR (NPDR), and 45 (21.3%) had proliferative DR (PDR). Forty-eight of 211 (22.7%) scans had diabetic macular edema (DME). The image processing method used significantly impacted values of VD, SVD, and FD (all P -values < 0.001). On multivariate analysis, the image processing method changed the clinical variables significantly associated with VD, SVD, and FD. However, BGS and CLAHE yielded more consistent significant covariates across multiple binarization algorithms. Conclusions: The image processing method can impact the conclusions of any given study analyzing quantitative OCTA metrics. Thus, caution is urged in the interpretation of such studies. Background subtraction or CLAHE may play a role in the standardization of image processing. Translational Relevance: This work proposes strategies to achieve robust and consistent analysis of OCTA imaging, which is especially important for clinical trials.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Algorithms , Cross-Sectional Studies , Diabetic Retinopathy/diagnostic imaging , Fluorescein Angiography/methods , Humans , Macular Edema/diagnostic imaging , Macular Edema/etiology , Retinal Vessels/diagnostic imaging , Retrospective Studies , Tomography, Optical Coherence/methods
4.
Am J Ophthalmol Case Rep ; 27: 101682, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35990800

ABSTRACT

Purpose: To describe an extrafoveal presentation of focal choroidal excavation and corresponding imaging findings. Methods: Retrospective case report. Patients: Single patient with diagnosis of extrafoveal focal choroidal excavation. Results: A 28-year-old man was referred for evaluation of a suspicious lesion in his right posterior fundus. Functional examination demonstrated best-corrected visual acuity of 20/40 in the right eye and 20/20 in the left eye. Ophthalmoscopy exam and fundus photography revealed a yellowish lesion superior to the fovea of the right eye. The lesion was hyperfluorescent on fundus autofluorescence imaging and late phase fluorescein angiography demonstrated staining of the lesion without leakage. Optical coherence tomography (OCT) of the lesion was consistent with focal choroidal excavation. Five months after presentation, the patient's vision, exam, and imaging remained stable. Discussion: Focal choroidal excavation is a recently recognized clinical entity that is often incidentally found, and presents asymptomatic or with mildly decreased visual acuity in the affected eye. It has characteristic findings on optical coherence tomography (OCT) that can be used to distinguish it from other retinal lesions that may appear similar on ophthalmoscopy. We present the case of an uncommon extrafoveal presentation of FCE at a relatively young age, which may represent either a congenital abnormality or the sequelae of an unidentified chronic process. While most FCE remain stable, patients are often followed for lesion progression and the possibility of choroidal vascular pathology which might necessitate intervention.

5.
Ophthalmology ; 129(12): 1412-1420, 2022 12.
Article in English | MEDLINE | ID: mdl-35792199

ABSTRACT

PURPOSE: To investigate the association of the Affordable Care Act (ACA) with nationwide eye-related emergency department (ED) use. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: All patients who presented to the ED with an eye-related primary diagnosis were eligible for inclusion. METHODS: Nationally representative data from the US Nationwide Emergency Department Sample were used to analyze eye-related ED visits before (2010-2013) and after (2014-2017) the ACA was mandated. All ED visits were categorized as emergent or nonemergent or could not be determined. MAIN OUTCOME MEASURES: The primary outcome was to compare the nationwide and regional incidence of eye-related ED visits per 100 000 US population before (2010-2013) and after (2014-2017) the ACA was mandated. Secondary outcome measures included change in payor status, proportion of urgent versus nonurgent visits, proportion of visits at teaching versus nonteaching hospitals, associated charges, and discharge disposition. RESULTS: A total of 16 808 343 eye-related ED visits occurred in the United States during the study period from 2010 to 2017. Of these, 8 088 203 ED visits occurred before the ACA was mandated (2010-2013), and 8 720 766 ED visits occurred after the ACA was mandated (2014-2017). After the ACA was mandated in 2014, there was an initial decline in incidence of eye-related ED visits from 652.4 per 100 000 population in 2013 to 593.0 per 100 000 population in 2014, followed by a rapid increase in incidence to 658.5 per 100 000 population in 2015, with a further increase to 746.6 per 100 000 population in 2016. The percentage of uninsured patients decreased from 19.0% to 14.3%. The increase in ED use was greatest for individuals in the lowest income quartile (895.1 per 100 000 population in 2013 to 964.0 per 100 000 in 2017). Overall, 44.8% of ED visits were due to nonemergent eye conditions. CONCLUSIONS: Although the ACA increased insurance coverage for Americans, theoretically increasing access to outpatient ophthalmic care, this did not decrease ED reliance for management of ophthalmic conditions. Additional measures beyond expanding insurance coverage may be necessary to provide high-quality, efficient, and equitable outpatient ophthalmic care to all Americans.


Subject(s)
Eye Diseases , Patient Protection and Affordable Care Act , Humans , United States/epidemiology , Retrospective Studies , Cross-Sectional Studies , Medically Uninsured , Emergency Service, Hospital , Insurance Coverage , Medicaid
6.
Stem Cells Transl Med ; 11(3): 269-281, 2022 03 31.
Article in English | MEDLINE | ID: mdl-35356975

ABSTRACT

Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE's apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE's basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.


Subject(s)
Biocompatible Materials , Macular Degeneration , Cell Transplantation , Humans , Macular Degeneration/metabolism , Retina/pathology , Retinal Pigment Epithelium/metabolism
7.
Graefes Arch Clin Exp Ophthalmol ; 260(3): 993-1004, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34605953

ABSTRACT

PURPOSE: This study aimed to evaluate posterior ocular structural and vascular changes in severe coronavirus disease 2019 (COVID-19) patients. METHODS: This was an observational, prospective, and controlled study including 106 eyes of 53 severe COVID-19 patients, compared to after recovery and 106 eyes of 53 age- and gender-matched healthy controls. All subjects were previously healthy adults and were assessed using spectral domain optical coherence tomography (SD-OCT) and ImageJ software. Subfoveal over a 1500-µm span and macular over a 6000-µm span cross-sectional areas of the vascular, stromal, and total choroid were measured. RESULTS: Of the 53 included patients, 28 (52.8%) were male, and 25 (47.2%) were female, with a mean age of 50.2 ± 7.4 years. In the active period of the disease, compared to after recovery and healthy controls, the outer plexiform layer thickness showed a significant increase (p = 0.004), and mean choroidal thickness was significantly higher (p < 0.0001); however, choroidal vascularity was significantly lower (p < 0.0001). The stromal area to vascular area (S/V) ratio of the choroid was significantly increased (p < 0.0001). All quadrants of the peripapillary retinal nerve fiber layer (RNFL) thicknesses were significantly increased (for all, p < 0.05). The reflectivity of OCT echo of the choroid and peripapillary RNFL was significantly higher (p = 0.023, p < 0.0001, respectively). CONCLUSION: This study detected significant posterior ocular structural and vascular alterations in patients with severe COVID-19 infections. These findings may be associated with direct host-virus interaction or linked to an autoimmune process, vasculopathy, or viral-mediated inflammation.


Subject(s)
COVID-19 , Adult , Choroid , Female , Humans , Male , Middle Aged , Nerve Fibers , Prospective Studies , Retinal Ganglion Cells , SARS-CoV-2 , Tomography, Optical Coherence/methods
8.
Circulation ; 145(2): 134-150, 2022 01 11.
Article in English | MEDLINE | ID: mdl-34743558

ABSTRACT

BACKGROUND: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. METHODS: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases-based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. RESULTS: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). CONCLUSIONS: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.


Subject(s)
Deep Learning/standards , Genome-Wide Association Study/methods , Genomics/methods , Mendelian Randomization Analysis/methods , Microvessels/pathology , Retina/metabolism , Female , Humans , Male , Middle Aged
9.
Transl Vis Sci Technol ; 10(12): 15, 2021 10 04.
Article in English | MEDLINE | ID: mdl-34647965

ABSTRACT

Purpose: To establish a continuous topography of retinal vessel density in normal eyes using optical coherence tomography angiography (OCTA). Methods: A retrospective chart review was performed, and 8-mm × 8-mm OCTA images from 22 normal eyes were analyzed. Vessel density was plotted as a continuous function of distance from the foveal center (radial vessel density) and directional meridians (directional vessel density) for the superficial capillary plexus and deep capillary plexus. Results: Continuous radial and directional vessel density plots for the superficial and deep capillary plexus were generated. Radial vessel density analysis revealed transition points at 657 microns (95% confidence interval [CI], 619-696) and 950 microns (95% CI, 903-997) from the foveal center for the superficial plexus and deep plexus, respectively. Directional vessel density analysis demonstrated significant vessel density variations in these vascular layers and provided greater detail compared to traditional quadrant analysis. Conclusions: There are significant topographic variations of retinal vessel density in normal eyes. Continuous vessel density analysis offers greater sensitivity in detecting topographic vessel density changes compared to traditional methods of analysis. Translational Relevance: This study establishes a normative continuous vessel density topography that may help elucidate the role of the vascular bed in different chorioretinal diseases.


Subject(s)
Microvascular Density , Tomography, Optical Coherence , Fluorescein Angiography , Retrospective Studies , Visual Acuity
10.
Ophthalmic Surg Lasers Imaging Retina ; 52(5): 281-287, 2021 05.
Article in English | MEDLINE | ID: mdl-34044717

ABSTRACT

BACKGROUND AND OBJECTIVE: To evaluate quantitative measurements of choroidal vasculature as obtained via ultra-widefield indocyanine green angiography (ICGA) in patients with systemic vascular diseases. PATIENTS AND METHODS: Retrospective chart review and image analysis of 38 eyes from 21 patients with ICGA as part of routine retinal care. Images were binarized with lines drawn at specific antero-posterior landmarks. The vessel density and mean vessel caliber were measured along these lines and correlated with systemic vascular disease status. RESULTS: Unlike those with other systemic vascular diseases, patients with obstructive sleep apnea (OSA) were found to have increased choroidal vascular density and vessel caliber in all measurements of the peripheral choroid compared with those patients without (P < .05 for all measurements). CONCLUSIONS: Patients with OSA may have increased vascular density secondary to increased choroidal vessel caliber. Further work is needed to validate the modeling and confirm the association. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:281-287.].


Subject(s)
Indocyanine Green , Vascular Diseases , Choroid , Coloring Agents , Fluorescein Angiography , Humans , Retrospective Studies
11.
Invest Ophthalmol Vis Sci ; 62(2): 14, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33591357

ABSTRACT

Purpose: Besides regulating paracellular diffusion, claudin-19 modulates the expression of proteins essential for the retinal pigment epithelium (RPE). This study asks how RPE responds when the expression of claudin-19 is reduced. Methods: In stem cell-derived RPE, claudin-19 and sequestosome-1/p62 (SQSTM1) were knocked down with siRNAs. Expression was monitored by quantitative RT-PCR and western blotting. Morphology and function were monitored by immunocytochemistry and transepithelial electrical resistance (TER). Phagocytosis of photoreceptor outer segments (POSs) was followed by fluorescence-activated cell sorting and western blotting. Pharmacology was used to assess the effects of AMP-activated protein kinase (AMPK) and SQSTM1 on phagocytosis. Enzymatic activity was measured using commercial assay kits. Results: Knockdown of claudin-19 reduced the TER without affecting the integrity of the apical junctional complex, as assessed by the distribution of zonula occludens-1 and filamentous actin. AMPK was activated without apparent effect on autophagy. Activation of AMPK alone had little effect on phagocytosis. Without affecting ingestion, knockdown reduced the rate of POS degradation and increased the steady-state levels of LC3B and SQSTM1. Proteasome inhibitors also retarded degradation, as did knockdown of SQSTM1. The expression of metallothioneins and the activity of superoxide dismutase increased. Conclusions: Knockdown of claudin-19 slowed the degradation of internalized POSs. The study questions the role of activated AMPK in phagocytosis and suggests a role for SQSTM1. Further, knockdown was associated with a partial oxidative stress response. The study opens new avenues of experimentation to explore these essential RPE functions.


Subject(s)
Claudins/genetics , Gene Expression Regulation , RNA/genetics , Retinal Diseases/genetics , Retinal Pigment Epithelium/metabolism , Sequestosome-1 Protein/genetics , Blotting, Western , Cell Line , Claudins/metabolism , Gene Knockdown Techniques , Humans , Immediate-Early Proteins , Immunohistochemistry , Microscopy, Confocal , Phagocytosis , Retinal Diseases/metabolism , Retinal Diseases/pathology , Retinal Pigment Epithelium/pathology , Sequestosome-1 Protein/biosynthesis
12.
Retina ; 41(2): 423-430, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-32467482

ABSTRACT

PURPOSE: To evaluate the visual outcome associated with intravitreal antibiotics (IVA) and pars plana vitrectomy (PPV) for acute postprocedure endophthalmitis. METHODS: Data from 237 eyes presenting with acute postprocedure endophthalmitis were collected from 57 retina specialists in 28 countries. All eyes were treated with IVA on the day of presentation. We classified eyes according to the method of treatment used as IVA and early PPV (IVA + PPV within 1 week of presentation) groups. RESULTS: After exclusion of ineligible eyes, data from 204 eyes were analyzed. The mean (SD) age of patients was 62.7 (21.8) years and 69.3 (12.7) years in the IVA and PPV groups, respectively (P = 0.18). Endophthalmitis secondary to cataract, intravitreal injections, PPV, and other intraocular procedures represented 64.2%, 16.2%, 13.7%, and 5.9% of cases, respectively. Intravitreal antibiotics alone were administered in 55 eyes (27.0%), and early PPV was performed in 149 eyes (73.0%). No difference was found between groups in the final visual acuity of ≥20/60 (43.6%, 65 eyes vs. 34.5%, 19 eyes) and ≤counting fingers (30.9%, 46 eyes vs. 36.4%, 20 eyes) for IVA versus early PPV groups, respectively. Vision of light perception (odds ratio = 12.2; 95% confidence interval: 2.0-72.6) and retinal detachment (odds ratio = 7.7; 95% confidence interval: 1.5-409) at baseline were predictive of vision of ≤counting fingers. Retinal detachment at baseline (odds ratio = 20.4; 95% confidence interval: 1.1-372.1) was predictive of final retinal detachment status. CONCLUSION: The current retrospective multicenter cohort of eyes with acute postprocedure endophthalmitis reports similar outcomes after treatment with IVA alone when compared with IVA and early PPV within 1 week of presentation.


Subject(s)
Anti-Bacterial Agents/adverse effects , Endophthalmitis/physiopathology , Eye Infections, Bacterial/physiopathology , Retinal Detachment/therapy , Visual Acuity , Vitrectomy/adverse effects , Acute Disease , Aged , Anti-Bacterial Agents/administration & dosage , Endophthalmitis/diagnosis , Endophthalmitis/etiology , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/etiology , Eye Infections, Bacterial/therapy , Female , Follow-Up Studies , Humans , Intravitreal Injections/adverse effects , Male , Middle Aged , Postoperative Complications , Retinal Detachment/diagnosis , Retrospective Studies , Silicone Oils/administration & dosage , Silicone Oils/adverse effects
13.
Retin Cases Brief Rep ; 15(1): 52-55, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-29474222

ABSTRACT

PURPOSE: To report a case of hemorrhagic occlusive retinal vasculitis after cataract surgery. METHODS: A 74-year-old woman presented with blurry vision and distorted vision, which started 2 days after an uncomplicated cataract surgery in the left eye. Intracameral vancomycin was injected during the case. The patient reported being treated with systemic vancomycin in the past. RESULTS: The visual acuity was 20/80 in the left eye. She had trace cells in the anterior chamber with no hypopyon and intraocular lens implant within the capsular bag in the left eye. Dilated fundus examination revealed no vitritis, There were large patches of peripheral retinal hemorrhages and retinal ischemia. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to hypersensitivity reaction to intracameral vancomycin. The patient was started on oral prednisone, and the topical difluprednate course was escalated. Within 3 weeks, vision improved to 20/30 in the left eye. She underwent pan retinal photocoagulation targeting the ischemic areas in the periphery. CONCLUSION: The patient had previous exposure to systemic vancomycin, which may have sensitized her immune system. Later on, the hypersensitivity reaction took place after exposure to intracameral vancomycin during cataract surgery. Our hemorrhagic occlusive retinal vasculitis case had a favorable visual outcome, and recognition of this entity will ensure that vancomycin will not be used for infection prophylaxis in the fellow eye at the time of cataract surgery.


Subject(s)
Cataract Extraction/adverse effects , Retinal Hemorrhage/chemically induced , Retinal Vasculitis/chemically induced , Retinal Vessels/pathology , Vancomycin/adverse effects , Visual Acuity , Administration, Oral , Aged , Female , Fluorescein Angiography/methods , Follow-Up Studies , Fundus Oculi , Glucocorticoids/administration & dosage , Humans , Injections, Intraocular/adverse effects , Laser Coagulation/methods , Prednisone/administration & dosage , Reoperation , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/therapy , Retinal Vasculitis/diagnosis , Retinal Vasculitis/therapy , Vancomycin/administration & dosage
15.
Invest Ophthalmol Vis Sci ; 61(13): 9, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33151282

ABSTRACT

Purpose: Many studies have demonstrated the ability of the retinal pigment epithelium (RPE) to foster the maturation of the developing retina. Few studies have examined the reciprocal effects of developing retina on the RPE. Methods: RPE isolated from human fetal RPE or differentiated from human stem cells was cultured on Transwell filter inserts. Retinal progenitor cells (RPCs) were differentiated from human stem cells and cultured on a planar scaffold composed of gelatin, chondroitin sulfate, hyaluronic acid, and laminin-521. Cultures were analyzed by quantitative RT-PCR, immunofluorescence, immunoblotting, and transepithelial electrical resistance (TER). Results: RPCs initially differentiated into several retina-like cell types that segregated from one another and formed loosely organized layers or zones. With time, the presumptive photoreceptor and ganglion cell layers persisted, but the intervening zone became dominated by cells that expressed glial markers with no evidence of bipolar cells or interneurons. Co-culture of this underdeveloped retinoid with the RPE resulted in a thickened layer of recoverin-positive cells but did not prevent the loss of interneuron markers in the intervening zone. Although photoreceptor inner and outer segments were not observed, immunoblots revealed that co-culture increased expression of rhodopsin and red/green opsin. Co-culture of the RPE with this underdeveloped retinal culture increased the TER of the RPE and the expression of RPE signature genes. Conclusions: These studies indicated that an immature neurosensory retina can foster maturation of the RPE; however, the ability of RPE alone to foster maturation of the neurosensory retina is limited.


Subject(s)
Cell Differentiation/physiology , Optic Nerve/cytology , Retina/cytology , Retinal Pigment Epithelium/cytology , Biomarkers/metabolism , Cells, Cultured , Coculture Techniques , Electric Impedance , Embryonic Stem Cells/cytology , Fluorescent Antibody Technique, Indirect , Genetic Markers/genetics , Humans , Immunoblotting , Optic Nerve/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Retina/metabolism , Retinal Pigment Epithelium/metabolism , Tissue Scaffolds
16.
Transl Vis Sci Technol ; 9(7): 22, 2020 06.
Article in English | MEDLINE | ID: mdl-32832228

ABSTRACT

Purpose: To evaluate the fractal dimension (Df ) of the choroidal vasculature using widefield indocyanine green (ICG) angiography and correlate it with the stage of age-related macular degeneration (AMD). Methods: Widefield ICG angiography performed on 38 eyes was retrospectively analyzed using the FracLac application within the National Institutes of Health ImageJ software to determine regional fractal dimensions in the macular field and widefield. These values were then associated with a diagnosis of no AMD, non-exudative AMD (subdivided into early/intermediate stage vs. advanced stage), or exudative AMD (subdivided into with or without geographic atrophy). The mean values were compared using Wilcoxon's test. Results: Early/intermediate non-exudative AMD and exudative AMD without geographic atrophy were found to have statistically significantly lower Df values compared to an absence of AMD when examining the macular field. Exudative AMD with geographic atrophy was found to have a statistically significant lower choroidal fractal dimension compared to no AMD when studied in the widefield. Conclusions: Advanced stages of macular degeneration were found to have significantly decreased the fractal dimensions of choroidal vasculature on widefield ICG compared to early/intermediate stages, possibly implying a generalized reduction in complexity and/or vessel caliber of the choroid with advancing stage of AMD. This finding agrees with previous understanding of the development of choriocapillaris atrophy in advanced macular degeneration. Translational Relevance: These findings suggest that using automated fractal analysis techniques can aid in differentiating stages of macular degeneration and, with further study, may be used to predict advancement of macular degeneration.


Subject(s)
Fractals , Macular Degeneration , Choroid/diagnostic imaging , Fluorescein Angiography , Humans , Macular Degeneration/diagnosis , Retrospective Studies , United States
17.
Exp Eye Res ; 198: 108157, 2020 09.
Article in English | MEDLINE | ID: mdl-32712183

ABSTRACT

Claudin-19 is the major claudin in the tight junctions of the retinal pigment epithelium (RPE). Claudin-3 is also uniformly expressed albeit in lesser amounts. Besides modulating transepithelial diffusion, claudins modulate gene expression. The absence of claudin-19 and claudin-3 in the RPE cell lines, ARPE-19 and hTERT-RPE-1, provide an opportunity to examine whether exogenous claudins regulate gene expression in the absence of tight junctions. Quantitative RT-PCR was used to compare gene expression in ARPE-19 and hTERT-RPE-1 with that of highly differentiated, human fetal RPE. Claudin-19 and claudin-3 were exogenously expressed using an adenoviral vector. The transepithelial electrical resistance (TER) was measured using Endohm electrodes, and the effects of claudin on the actin cytoskeleton were determined by immunocytochemistry. The effect of claudin on gene expression was examined by quantitative RT-PCR and western blotting. Aside from claudin-19 and claudin-3, ARPE-19 and hTERT-RPE-1 expressed most junction-associated mRNAs in amounts comparable to human fetal RPE, but some RPE signature and maturation genes were under-expressed. Unlike ARPE-19, hTERT-RPE-1 failed to form tight junctions or develop a TER. Claudins exogenously expressed in hTERT-RPE-1 failed to crystalize an apical junctional complex. Actin filaments were not redistributed from stress fibers to cortical bands, and a TER was not established. In hTERT-RPE-1, claudins were found only in internal vesicular-like structures. Nonetheless, claudins increased the expression of the mRNAs for a collection of RPE-enriched proteins. Claudin-19 and claudin-3 had different effects on gene and protein expression indicating activation of overlapping, but distinct, signaling pathways. A major difference was the ability of claudin-19 to affect steady-state levels of ADAM9 and tyrosinase in ARPE-19. In conclusion, claudins can increase the barrier function of a pre-existing apical junctional complex, but on its own it cannot recruit tight junction proteins to form a complex de novo. Many effects of claudin on gene expression did not require an association with the apical junctional complex. Although claudin-19 shared many effects with claudin-3, claudin-19 exerted unique effects on the maturation of RPE.


Subject(s)
Claudins/genetics , Gene Expression , Membrane Proteins/genetics , RNA, Messenger/genetics , Retinal Pigment Epithelium/metabolism , Blotting, Western , Cells, Cultured , Claudins/biosynthesis , Humans , Membrane Proteins/biosynthesis , Retinal Pigment Epithelium/cytology , Tight Junctions/metabolism
18.
J Ocul Pharmacol Ther ; 36(7): 534-539, 2020 09.
Article in English | MEDLINE | ID: mdl-32609038

ABSTRACT

Purpose: The purpose of this study was to report the clinical etiologies, microbial spectrum, antibiotic resistance, and visual acuity (VA) outcomes associated with acute endophthalmitis. Methods: A retrospective chart review of patients with International Classification of Diseases (ICD)-9 and ICD-10 codes for endophthalmitis over a 6-year period (2011-2016) at a tertiary referral center was performed. The clinical records were reviewed to evaluate clinical etiologies, microbial spectrum, antibiotic susceptibilities and resistance, and visual outcomes. Results: Medical records of 94 patients treated for culture-proven endophthalmitis were reviewed. The etiologies of endophthalmitis were exogenous in 68.8% of cases and endogenous in 31.2% of cases. The most common inciting factors for exogenous endophthalmitis were progression of corneal ulcer and postoperative infection after cataract extraction. The microbial spectrum of causative organisms was dominated by coagulase-negative Staphylococcus (30.9%), followed by Staphylococcus aureus (23.4%). The most frequent fungal isolates were Candida species. Antibiotic susceptibilities of gram-positive bacteria ranged from 96.7% for vancomycin to 28.8% for penicillin G. Antibiotic susceptibilities of gram-negative bacteria were overall very high, with >90% susceptibility among isolated culture samples. Final VA outcomes of 20/400 or better were reported in 62.5% of patients. Conclusions: The study demonstrates that the most frequent clinical etiology of endophthalmitis was exogenous due to progression of corneal ulcer and postoperative infection after cataract extraction. The spectrum of pathogens causing endophthalmitis is composed of mainly Gram-positive organisms (particularly coagulase-negative Staphylococcus). VA was improved in the majority of patients after treatment for endophthalmitis.


Subject(s)
Endophthalmitis/drug therapy , Eye Infections, Bacterial/drug therapy , Eye Infections, Fungal/drug therapy , Acute Disease , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , Endophthalmitis/epidemiology , Endophthalmitis/microbiology , Eye Infections, Bacterial/epidemiology , Eye Infections, Bacterial/microbiology , Eye Infections, Fungal/epidemiology , Eye Infections, Fungal/microbiology , Fungi/drug effects , Fungi/isolation & purification , Humans , Microbial Sensitivity Tests , Retrospective Studies , Visual Acuity/drug effects
19.
Am J Ophthalmol ; 218: 128-135, 2020 10.
Article in English | MEDLINE | ID: mdl-32445703

ABSTRACT

PURPOSE: To describe temporal and geographic trends in the US eye care workforce. DESIGN: Cross-sectional study. METHODS: We obtained data from the 2017 Area Health Resources File. The main outcomes were ophthalmologist and optometrist density, as defined as the number of providers per 100,000 individuals, the ratio of ophthalmologists ≥55 years of age to those <55 years of age, and county characteristics associated with the availability of an ophthalmologist. RESULTS: From 1995 to 2017, the national ophthalmologist density decreased from 6.30 to 5.68 ophthalmologists per 100,000 individuals. Although rural counties experienced a mean annual increase in ophthalmologist density by 2.26%, they still had a lower mean ophthalmologist density (0.58/100,000 individuals) compared with nonmetropolitan (2.19/100,000 individuals) and metropolitan counties (6.29/100,000 individuals) in 2017. The ratio of older to younger ophthalmologists increased from 0.37 in 1995 to 0.82 in 2017, with the greatest ratio increase occurring in rural counties (0.29 to 1.90). The presence of an ophthalmologist was significantly associated with a greater proportion of individuals with a college degree and health insurance, and more developed health care infrastructure. From 1990 to 2017, the density of optometrists increased from 11.06 to 16.16 optometrists per 100,000 individuals. CONCLUSIONS: Over the last 2 decades, the national density of ophthalmologists has decreased and the workforce has aged. In contrast, the density of optometrists has increased. Rural counties continue to have a disproportionately lower supply of eye care providers, although some growth has occurred. Given the rising ratio of optometrists to ophthalmologists, it is of interest for future work to determine how the optometrist workforce can best complement potential shortages of ophthalmologists.


Subject(s)
Health Workforce/statistics & numerical data , Ophthalmologists/trends , Optometrists/trends , Adult , Age Distribution , Aged , Cross-Sectional Studies , Female , Health Services Accessibility/statistics & numerical data , Health Services Needs and Demand/statistics & numerical data , Health Workforce/trends , Humans , Male , Middle Aged , Ophthalmologists/statistics & numerical data , Optometrists/statistics & numerical data , Physicians, Women/statistics & numerical data , Physicians, Women/trends , Rural Population/statistics & numerical data , Sex Distribution , United States/epidemiology , Urban Population/statistics & numerical data
20.
Eye (Lond) ; 34(5): 825-834, 2020 05.
Article in English | MEDLINE | ID: mdl-32313173

ABSTRACT

BACKGROUND/OBJECTIVES: To evaluate the efficacy and safety of pars plana vitrectomy for symptomatic floaters. SUBJECTS/METHODS: Forty-eight vitreoretinal surgeons from 16 countries provided information on 581 eyes who underwent vitrectomy for floaters in this retrospective survey study conducted by European VitreoRetinal Society. Percentage symptomatic improvement, incidence of retinal tears/detachment and post-vitrectomy cataract surgery, and the factors associated with satisfaction and complications were investigated. RESULTS: Ninety-two percent were satisfied with the results, with 86.3% reporting complete resolution of daily-life symptoms. Overall satisfaction was lower in patients with smaller vitreous opacities at presentation (OR:0.4). Iatrogenic retinal breaks occurred in 29 eyes (5%). Core vitrectomy and cut rates of 1500-4000 or >4000 cuts/min were associated with lower risk of retinal breaks than complete vitrectomy (OR:0.05) and cut rates < 1500 cuts/min (OR: 0.03, 0.12, respectively). Fourteen eyes (2.4%) developed retinal detachment at a median of 3 months; and 84 (48.6%) developed cataract at a median of 16 months post-vitrectomy. CONCLUSIONS: Pars plana vitrectomy resulted in high patient satisfaction with relatively low rate of severe complications in a large group of patients. The procedure may be safer when core vitrectomy and cut rates > 1500 cuts/min are favoured. Proper patient selection and informed consent are the most important aspects of surgery.


Subject(s)
Retinal Detachment , Retinal Perforations , Humans , Postoperative Complications/epidemiology , Retinal Detachment/surgery , Retinal Perforations/surgery , Retrospective Studies , Vitrectomy , Vitreous Body/surgery
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