Macular Xanthophylls and Markers of the Anterior Visual Pathway among Persons with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) can cause retinal thinning among persons with MS with optic neuritis (MS-ON). Macular xanthophylls are carotenoids that comprise the macular pigment, filtering blue light and countering photo-oxidation. However, macular xanthophyll status and its implications for markers of neuroaxonal degeneration have not been examined in MS. OBJECTIVES: This study characterized differences in macular and serum xanthophylls, and retinal morphometry [retinal nerve fiber layer thickness at the macular (mRNFL) and optic disc (odRNFL) and total macular volume (TMV)] in individuals with MS and healthy controls (HC). Associations between macular pigment optical density (MPOD) and retinal morphometry were also examined. METHODS: Adults aged 45-64 y (HC, n = 42; MS, n = 40) participated in a cross-sectional study. MPOD was measured via heterochromatic flicker photometry. Retinal morphometry was measured via optical coherence tomography (OCT). Serum carotenoids were quantified using HPLC. Dietary carotenoids were collected using 7-d records. One-factor ANOVA was conducted to determine group effects on macular, serum, and dietary carotenoids. Partial correlations examined the relations between MPOD, retinal morphometry, diet, and serum carotenoids. RESULTS: Relative to HC, persons with MS-ON had lower MPOD (Cohen's d = 0.84, P = 0.014), lower odRNFL (Cohen's d = 2.16, P <0.001), lower mRNFL (Cohen's d = 0.57, P = 0.028), and lower TMV (Cohen's d = 0.95, P = 0.011). MS without ON (MS) had lower odRNFL (Cohen's d = 0.93, P = 0.001) than HC and lower serum lutein than MS-ON subjects (Cohen's d = 0.65, P = 0.014). Among MS, MPOD was positively correlated with odRNFL thickness (ρ = 0.43, P = 0.049) and TMV (ρ = 0.45, P = 0.039), whereas odRNFL was negatively correlated with serum lutein (ρ = -0.68, P = 0.016) and zeaxanthin (ρ = -0.62, P = 0.028). CONCLUSIONS: Persons with MS-ON exhibited poorer xanthophyll status in the macula and serum. MPOD was associated with beneficial anatomical features in the MS group. These findings warrant confirmation with larger cohorts and prospective trials to evaluate xanthophyll effects on the anterior visual pathway in MS.

Effect of telephone calls from a centralized coordinating center on participant retention in a randomized clinical trial.

BACKGROUND/AIMS: In clinical trials, participant retention is critical to reduce bias and maintain statistical power for hypothesis testing. Within a multi-center clinical trial of diabetic retinopathy, we investigated whether regular phone calls to participants from the coordinating center improved long-term participant retention. METHODS: Among 305 adults in the Diabetic Retinopathy Clinical Research Retina Network Protocol S randomized trial, 152 participants were randomly assigned to receive phone calls at baseline, 6 months, and annually through 3 years (annual contact group) while 153 participants were assigned to receive a phone call at baseline only (baseline contact group). All participants could be contacted if visits were missed. The main outcomes were visit completion, excluding deaths, at 2 years (the primary outcome time point) and at 5 years (the final time point). RESULTS: At baseline, 77% (117 of 152) of participants in the annual contact group and 76% (116 of 153) in the baseline contact group were successfully contacted. Among participants in the annual contact group active at each annual visit (i.e. not dropped from the study or deceased), 85% (125 of 147), 79% (108 of 136), and 88% (110 of 125) were contacted successfully by telephone around the time of the 1-, 2-, and 3-year visits, respectively. In the annual and baseline contact groups, completion rates for the 2-year primary outcome visit were 88% (129 of 147) versus 87% (125 of 144), respectively, with a risk ratio of 1.01 (95% confidence interval: 0.93-1.10, p = .81). At 5 years, the final study visit, participant completion rates were 67% (96 of 144) versus 66% (88 of 133) with a risk ratio of 1.01 (95% confidence interval = 0.85-1.19, p = .93). At 2 years, the completion rate of participants successfully contacted at baseline was 89% (202 of 226) versus 80% (52 of 65) among those not contacted successfully (risk ratio = 1.12, 95% confidence interval = 0.98-1.27, p = .09); at 5 years, the completion percentages by baseline contact success were 69% (148 of 213) versus 56% (36 of 64; risk ratio = 1.24, 95% confidence interval = 0.98-1.56, p = .08). CONCLUSION: Regular phone calls from the coordinating center to participants during follow-up in this randomized clinical trial did not improve long-term participant retention.

Investigation of Needle Characteristics Using an Animal Model for Improved Outcomes in Anterior Chamber Paracentesis.

Background/Aims: The current standard of care to perform an anterior chamber paracentesis involves the use of a multipurpose market needle and syringe. The use of standard needles for this purpose may result in injury to the patient due to increased force with insertion and increased globe displacement during the procedure. This research investigates the current market needle characteristics and the impact of each needle characteristic on force. Methods: Several comparative trials were conducted to evaluate the needles. Needle characteristics of interest were gauge, primary bevel angle, number of bevels in the lancet, and needle hub geometry. Measurements of corneal insertion forces were made using a synthetic thermoplastic polyurethane medium, and bovine and porcine models. Needle safety was investigated with corneal abrasion experiments. Results: Reduced insertion force was observed with lower lancet primary angle. There was no difference based on the number of bevels in the lancet. Rounded hub geometry had minimal distribution to the corneal epithelium. Conclusions: Needle characteristics impact the force needed for needle insertion into the tissue. Since higher force can lead to increased risk and less efficiency during the procedure, reducing this force may improve the outcomes of the procedure. Needle entry can be reduced by designing an improved needle that includes a lower gauge and reduced primary angle of the lancet.

NanoLC-timsTOF-Assisted Analysis of Glycated Albumin in Diabetes-Affected Plasma and Tears.

Glycation is a spontaneous and nonenzymatic glycosylation. Glycated albumin (GA), which serves as an important biomarker in plasma in the diagnosis and characterization of diabetes, can be passively filtered from the plasma to tears. Tears are important targets for research in clinical diagnostics due to the ability to collect this biofluid noninvasively and repeatably. Therefore, the analysis of GA in tear film provides information for monitoring diabetes progression independent of blood pathologies. Due to the limited volume (1-5 µL) of natural tear film, we developed a small volume assay using a nano liquid chromatography-trapped ion mobility spectrometry-time-of-flight MS (nanoLC-timsTOF) platform for the analysis of glycated albumin in human plasma and tear films affected by diabetes. The peptides containing lysine 525, which is the main glycation site in GA, were relatively quantified and represented as the GA level. The results of the measurements showed that GA levels were significantly higher in diabetes-affected plasma and tears compared to controls with a p-value < 0.01. A strong correlation of glycated albumin levels was observed for the plasma and tear film in diabetes samples (Pearson coefficient 0.92 with a p-value 0.0012). Moreover, the number of GA glycation sites was significantly higher in diabetes-affected plasma and tear comparatively to controls. Among all the glycation sites in plasma albumin, the GA level quantified by lysine 136/137 had a strong correlation with more commonly used lysine 525, suggesting that lysine 136 /137 is an alternative diabetes biomarker in plasma. Overall, our findings demonstrate GA in tears as a biomarker for monitoring diabetes progression, highlighting new possibilities for quick and noninvasive diabetes detection and monitoring.

Use of Adjunctive Corticosteroid With Antivascular Endothelial Growth Factor Agents in the Treatment of Choroidal Neovascular Membrane Associated With Presumed Ocular Histoplasmosis.

Purpose: To evaluate the impact of combination treatment of antivascular endothelial growth factor (anti-VEGF) intravitreal injections and corticosteroids in patients with choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). Methods: A retrospective multicenter study was conducted in a cohort from Illinois and Missouri. Patients were identified over an 8-year period, and data were evaluated over a 1-year study window commencing with treatment initiation. Group 1 included patients treated with intravitreal injections of anti-VEGF, and group 2 included those who received intravitreal injections of anti-VEGF and adjuvant corticosteroids. Optical coherence tomography (OCT) measurements and increases in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score were compared between each group. Results: Using the method of last visit carried forward, the visual acuity (VA) in group 2 was 6.42 ETDRS letters better than the VA in group 1 at the final assessment. Patients in group 2 had a mean ETDRS letter gain of 21.50 (P = .06) from the initial baseline vision. The average amount of decrease in OCT central subfield thickness compared with baseline was lower in group 1 (80.9 ± 129.8 µm) vs group 2 (102.8 ± 90.40 µm) at the 1-year follow-up visit (P = .25). Conclusions: Approved treatment of CNV secondary to POHS is limited. Adjuvant corticosteroid treatment in patients with CNV secondary to POHS may provide better long-term vision and OCT outcomes than anti-VEGF alone and may offer an additional therapy option for these patients.

An Atypical Presentation of Propionibacterium Acnes Endophthalmitis Following Cataract Surgery.

Purpose: To describe a case with an unusual presentation of Propionibacterium acnes (P acnes) with ultimately a good visual outcome. Methods: A case report with review of approaches to P acnes endophthalmitis. Results: We describe a patient with an unusual presentation of P acnes of panuveitis with white, circular preretinal lesions without intracapsular deposits. Diagnosis was made from cultures from pars plana vitrectomy. Eventually, she was definitively managed with capsulectomy, repositioning of her intraocular lens via sutureless intrascleral fixation, and intravitreal vancomycin injection. Conclusion: This is a report of P acnes endophthalmitis presenting with discrete preretinal lesions where surgical and medical management lead to a complete resolution of uveitis and symptoms after a 3-year follow up where the patient's final visual acuity was Snellen 20/20 OU.

In situ plasmonic generation in functional ionic-gold-nanogel scaffold for rapid quantitative bio-sensing.

Conventional analytical techniques, which have been developed for high sensitivity and selectivity for the detection and quantification of relevant biomarkers, may not be as suitable for medical diagnosis in resource scarce environments as compared to point-of-care devices (POC). We have developed a new reactive sensing material which contains ionic gold entrapped within an agarose gel scaffold for POC quantification of ascorbic acid (AA) in tear fluid. Pathologically elevated concentration of AA in human tear fluid can serve as a biomarker for full-thickness injuries to the ocular surface, which are a medical emergency. This reactive sensing material will undergo colorimetric changes, quantitatively dependent on endogenous bio-reductants that are applied, as the entrapped ionic gold is reduced to form plasmonic nanoparticles. The capacity for this reactive material to function as a plasmonically driven biosensor, called 'OjoGel' (ojo-eye), was demonstrated with the endogenous reducing agent, AA. Through applications of AA of varied concentrations to the OjoGel, we demonstrated a quantitative colorimetric relationship between red (R) hexadecimal values and concentrations of AA in said treatments. This colorimetric relationship is directly resultant of plasmonic gold nanoparticle formation within the OjoGel scaffold. Using a commercially available mobile phone-based Pixel Picker® application, the OjoGel plasmonic sensing platform opens a new avenue for easy-to-use, rapid, and quantitative biosensing with low cost and accurate results.

Ratiometric analysis of optical coherence tomography-measured in†vivo retinal layer thicknesses for the detection of early diabetic retinopathy.

Influence of diabetes mellitus (DM) and diabetic retinopathy (DR) on parafoveal retinal thicknesses and their ratios was evaluated. Six retinal layer boundaries were segmented from spectral-domain optical coherence tomography images using open-source software. Five study groups: (1) healthy control (HC) subjects, and subjects with (2) controlled DM, (3) uncontrolled DM, (4) controlled DR and (5) uncontrolled DR, were identified. The one-way analyses of variance (ANOVA) between adjacent study groups (i. e. 1 with 2, 2 with 3, etc) indicated differences in retinal thicknesses and ratios. Overall retinal thickness, ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness, and their combination (GCL+ IPL), appeared to be significantly less in the uncontrolled DM group when compared to controlled DM and controlled DR groups. Although the combination of nerve fiber layer (NFL) and GCL, and IPL thicknesses were not different, their ratio, (NFL+GCL)/IPL, was found to be significantly higher in the controlled DM group compared to the HC group. Comparisons of the controlled DR group with the controlled DM group, and with the uncontrolled DR group, do not show any differences in the layer thicknesses, though several significant ratios were obtained. Ratiometric analysis may provide more sensitive parameters for detecting changes in DR. Picture: A representative segmented OCT image of the human retina is shown.

A Case of Unilateral Optic Neuropathy Following Influenza Vaccination.

The influenza vaccination has greatly benefited public health, leading to significant reductions in flu season hospitalizations and deaths. However, with more widespread administration of this vaccine, it is expected that the absolute number of patients that present with unusual, adverse reactions will increase. Here, we report a case of a 55-year-old woman who developed a progressive optic neuropathy and severe visual loss associated with optic disc edema following influenza virus vaccination. Our patient also experienced other concurrent symptoms, including bilateral knee effusions, muscle spasms and a facial rash. The strong temporal connection between the vaccine administration and the development of sequelae suggests that the optic neuropathy was an adverse reaction. Furthermore, HLA typing of our patient revealed alleles that have been linked to autoimmune reactions, consistent with the notion that specific HLA alleles could be involved in the pathophysiology of these adverse reactions.

Real-Time Monitoring of Post-Surgical and Post-Traumatic Eye Injuries Using Multilayered Electrical Biosensor Chip.

Lack of current techniques for the early monitoring of bleb leaks and other post-traumatic or post-surgical ocular injury has posed an unmet clinical need for the development of new techniques. Present evaluation techniques use either subjective or nonquantitative approaches. At present, there are no FDA approved ocular devices that can directly measure ascorbic acid (AA) concentration levels for both tear film (TF) and aqueous humor (AH) at point-of-care (POC) level. Toward this aim, we present a novel POC quantitative assay, called the ocular biosensor device, which can be used to evaluate the integrity of the anterior surface of the eye by measuring the concentration of AA in TF and AH. Herein, we utilize a novel scientific engineering approach for the development of a disposable paper based POC ocular biosensor strip. A grafted poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) and graphene platelet composite with contour based µ-electrodes design (CBµE) exhibit a highly sensitive platform to perform electrochemical immunosensing technique to study clinical samples that have small volumes like tear fluid. Samples used in this study were collected clinically from subjects undergoing therapeutic anterior chamber paracentesis. The proposed biosensor reports the level of AA concentration on an electronic screen, making the results easy to read, efficient, and reliable.

A case of recurrent, self-inflicted handheld laser retinopathy.

A 17-year-old young man presented with vision loss and discrete, bilateral foveal lesions. The patient returned 6 weeks later with worsening vision, prominent bilateral retinal lesions, and a full-thickness macular hole in the right eye consistent with recurrent self-inflicted handheld laser retinopathy. After instructing the family to remove the patient's access to laser pointers, follow-up examination revealed spontaneous closure of the macular hole but minimal vision improvement. Recurrent ocular exposure to handheld lasers can masquerade as an organic process in patients who withhold pertinent history. Clinicians should rely on the distinguishing features seen on examination and multimodal imaging to make the diagnosis of handheld laser retinopathy.

IMAGING WITH MULTIMODAL ADAPTIVE-OPTICS OPTICAL COHERENCE TOMOGRAPHY IN MULTIPLE EVANESCENT WHITE DOT SYNDROME: THE STRUCTURE AND FUNCTIONAL RELATIONSHIP.

PURPOSE: To elucidate the location of pathological changes in multiple evanescent white dot syndrome (MEWDS) with the use of multimodal adaptive optics (AO) imaging. METHODS: A 5-year observational case study of a 24-year-old female with recurrent MEWDS. Full examination included history, Snellen chart visual acuity, pupil assessment, intraocular pressures, slit lamp evaluation, dilated fundoscopic exam, imaging with Fourier-domain optical coherence tomography (FD-OCT), blue-light fundus autofluorescence (FAF), fundus photography, fluorescein angiography, and adaptive-optics optical coherence tomography. RESULTS: Three distinct acute episodes of MEWDS occurred during the period of follow-up. Fourier-domain optical coherence tomography and adaptive-optics imaging showed disturbance in the photoreceptor outer segments (PR OS) in the posterior pole with each flare. The degree of disturbance at the photoreceptor level corresponded to size and extent of the visual field changes. All findings were transient with delineation of the photoreceptor recovery from the outer edges of the lesion inward. Hyperautofluorescence was seen during acute flares. Increase in choroidal thickness did occur with each active flare but resolved. CONCLUSION: Although changes in the choroid and RPE can be observed in MEWDS, Fourier-domain optical coherence tomography, and multimodal adaptive optics imaging localized the visually significant changes seen in this disease at the level of the photoreceptors. These transient retinal changes specifically occur at the level of the inner segment ellipsoid and OS/RPE line. En face optical coherence tomography imaging provides a detailed, yet noninvasive method for following the convalescence of MEWDS and provides insight into the structural and functional relationship of this transient inflammatory retinal disease.

Point-of-service, quantitative analysis of ascorbic acid in aqueous humor for evaluating anterior globe integrity.

Limited training, high cost, and low equipment mobility leads to inaccuracies in decision making and is concerning with serious ocular injuries such as suspected ruptured globe or post-operative infections. Here, we present a novel point-of-service (POS) quantitative ascorbic acid (AA) assay with use of the OcuCheck Biosensor. The present work describes the development and clinical testing of the paper-based biosensor that measures the changes in electrical resistance of the enzyme-plated interdigitated electrodes to quantify the level of AA present in ocular fluid. We have demonstrated the proof-of-concept of the biosensor testing 16 clinical samples collected from aqueous humor of patients undergoing therapeutic anterior chamber paracentesis. Comparing with gold standard colorimetric assay for AA concentration, OcuCheck showed accuracy of >80%, sensitivity of >88% and specificity of >71%. At present, there are no FDA-approved POS tests that can directly measures AA concentration levels in ocular fluid. We envisage that the device can be realized as a handheld, battery powered instrument that will have high impact on glaucoma care and point-of-care diagnostics of penetrating ocular globe injuries.

Retinal imaging with en face and cross-sectional optical coherence tomography delineates outer retinal changes in cancer-associated retinopathy secondary to Merkel cell carcinoma.

BACKGROUND: The study aims to correlate Fourier-domain optical coherence tomography (FD-OCT) with Goldmann visual field (GVF) to show the photoreceptor (PR) structure and function relationship in the first described case of cancer-associated retinopathy (CAR) from Merkel cell carcinoma. FINDINGS: A case study of a patient with CAR who was imaged with serial GVF and FD-OCT over a 2-year period was carried out. En face images were created using a custom algorithm from the volumetric Fourier-domain OCT scans at the PR level. The areas of decreased PR reflectivity on the en face images were compared with GVF obtained at the same time point. Regions of reduced signal on en face scans corresponded with the position and shape of the GVF scotomas. Initially, the vision improved without PR changes. Cross-sectional OCTs showed early recovery of the outer nuclear layer and later improvement in the nerve fiber layer. Worsening vision corresponded with recurrence of the underlying cancer. Progressive global retinal atrophy was seen over time. CONCLUSIONS: Merkle cell carcinoma can cause CAR. Retinal function recovered without structural PR recovery. Transient vision improvements in treated CAR patients may be due to layers other than the PRs, but eventual vision decline results from significant progressive retinal atrophy.

Rapid resolution of macular edema associated with central retinal vein occlusion using ranibizumab after failure with multiple bevacizumab injections.

PURPOSE: To report improvement in cystoid macular edema from central retinal vein occlusion with one injection of ranibizumab after failure with seven injections of bevacizumab. METHODS: Case report. RESULTS: A 74-year-old female developed persistent blurred vision for three months. Ocular examination revealed macular edema secondary to nonischemic central retinal vein occlusion. The patient was treated with intravitreal bevacizumab (1.25 mg in 0.05 mL). She received seven injections (every 5-6 weeks). Vision fluctuated between 20/30 and 20/60 with minimal variation in central foveal thickness (449-574 µm). However, weeks after one injection of ranibizumab the patient's vision improved to 20/20 with near resolution of macular edema (CFT = 343 µm). CONCLUSIONS: Patients with no response to bevacizumab injections can show a rapid and large improvement with ranibizumab. This underscores the important differences between these two medications. Further study is required to determine if these initial effects of ranibizumab can be maintained.

Marathon runner's retinopathy.

PURPOSE: To report a case of an unusual retinopathy in an otherwise healthy 25-year-old marathon runner. METHODS: Case report. RESULTS: A 25-year-old female marathon runner developed sudden onset of monocular vision loss during a routine training run. The retinal features included a large, central, subhyaloid hemorrhage, multiple intraretinal hemorrhages, disc edema and venous dilation and tortuosity resembling characteristics of both valsalva retinopathy and nonischemic central retinal vein occlusion. Work up for underlying systemic cause was negative. However, the patient did participate in endurance exercise. CONCLUSION: Strenuous exercise increases activated platelets and other clotting factor elements. During exercise, this increase in clotting factors in the coagulation cascade is usually balanced by activation of key elements in the fibrinolysis cascade as well. However, certain individuals, especially those who already have a predisposition to clotting or other thrombogenic risk factors may disrupt the balance between coagulation and fibrinolysis during strenuous exercise favoring coagulation which places them at risk for thrombus formation.

Chronic retinal detachment with secondary retinal macrocyst and peripheral neovascularization.

PURPOSE: To report the association of a retinal macrocyst with peripheral retinal neovascularization that occurred secondary to a chronic, subclinical rhegmatogenous retinal detachment and to illustrate the utility of wide-field fundus photography. METHODS: Case Report. RESULTS: A 37 year-old male was diagnosed with chronic retinal detachment on routine eye examination. Further evaluation revealed intraretinal hemorrhages and a retinal macrocyst. Diagnosis was confirmed with wide-field fundus photography and fluorescein angiography. Surgery was recommended to repair the retinal detachment, to allow spontaneous resolution of the macrocyst. CONCLUSION: Chronic, subclinical retinal detachments may rarely be associated with retinal macrocysts and retinal neovascularization. This altered retinal morphology can be delineated on wide-field fundus imaging, which aids in diagnosis and management.

Reverse magnetic resonance signal from intraocular hemorrhage.

PURPOSE: To report the effect of massive intraocular hemorrhage on magnetic resonance imaging signal. METHODS: Case report. RESULTS: A 34-year-old power weightlifter developed sudden, nontraumatic loss of vision to no light perception in his right eye. Magnetic resonance imaging (MRI) revealed homogeneous bright signal on T1-weighted images and dark signal on T2-weighted images, opposite the signal of his normal left eye. These findings were suggestive of subacute massive intraocular hemorrhage. The patient elected enucleation for the blind, painful eye. The diagnosis made by MRI signal interpretation was confirmed by subsequent histopathology analysis. CONCLUSION: Based on hemoglobin degradation products, MRI can assist in judging the stage of blood breakdown and diagnosing intraocular pathology.