Imaging human macular pigments with visible light optical coherence tomography and superluminescent diodes.

We demonstrate superluminescent diodes (SLDs) for visible light optical coherence tomography (OCT) of the human retina. SLDs are less costly than supercontinuum sources and have lower intrinsic excess noise, enabling imaging closer to the shot noise limit. While single SLDs are not broadband, they provide power concentrated at specific wavelengths relevant to retinal function. As a new, to the best of our knowledge, application, we image human macular pigments (MPs), which are thought to both aid vision and protect against advanced age-related macular degeneration. Using the unique depth-resolved capabilities of OCT, we localize MPs in depth to Henle's fibers beneath the foveal pit in the living human retina. Our approach reduces the cost of visible light OCT to nearly that of near-infrared (NIR) OCT while also providing information about clinically relevant MPs which cannot be measured in the NIR.

Gender Compensation Gap for Ophthalmologists in the First Year of Clinical Practice.

PURPOSE: To identify the role of gender and other factors in influencing ophthalmologists' compensation. DESIGN: Cross-sectional study. PARTICIPANTS: U.S. practicing ophthalmologists. METHODS: Between January and March 2020, an anonymous survey was sent to U.S. residency program directors and practicing ophthalmologists who recently completed residency training. Respondents who completed residency ≤ 10 years ago and responded to questions about gender, fellowship training, state of practice, and salary were included. Propensity score match (PSM) analysis was performed with age, academic residency, top residency, fellowship, state median wage, practice type, ethnicity, and number of workdays. Multivariate linear regression (MLR) analysis controlled for additional factors along with the aforementioned variables. MAIN OUTCOME MEASURES: Base starting salary with bonus (SWB) received in the first year of clinical position was the main outcome measure. A multiplier of 1.2 (20%) was added to the base salary to account for bonus. RESULTS: Of 684 respondents, 384 (56% were female, 44% were male) from 68 programs were included. Female ophthalmologists received a mean initial SWB that was $33 139.80 less than that of their male colleagues (12.5%, P = 0.00). The PSM analysis showed an SWB difference of -$27 273.89 (10.3% gap, P = 0.0015). Additionally, SWB differences were calculated with the number of workdays substituted by operating room (OR) days (-$27 793.67 [10.5% gap, P = 0.0013]) and clinic days (-$23 597.57 [8.90% gap, P = 0.0064]) in separate PSM analyses. The SWB differences between genders were significant using MLR analyses, which also controlled for work, clinic, and OR days separately (-$22 261.49, $-18 604.65, and $-16 191.26, respectively; P = 0.017, P = 0.015, P = 0.002, respectively). Gender independently predicted income in all 3 analyses (P < 0.05). Although an association between gender and the attempt to negotiate was not detected, a greater portion of men subjectively reported success in negotiation (P = 0.03). CONCLUSIONS: Female ophthalmologists earn significantly less than their male colleagues in the first year of clinical practice. Salary differences persist after controlling for demographic, educational, and practice type variables with MLR and PSM analyses. These income differences may lead to a substantial loss of accumulated earnings over an individual's career.

POSITION OF IN-THE-BAG POSTERIOR CHAMBER INTRAOCULAR LENSES RELATIVE TO THE LIMBUS: Applications to Scleral-Sutured Lenses.

PURPOSE: To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. METHODS: This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. RESULTS: A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. CONCLUSION: True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.

ASSESSING THE ABILITY OF PREOPERATIVE QUANTITATIVE SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS TO PREDICT VISUAL OUTCOME IN IDIOPATHIC MACULAR HOLE SURGERY.

PURPOSE: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Another 'BEE'? - Brain-Eye-Ear (BEE) Disease Secondary to HbSC Disease Masquerading as Multiple Sclerosis.

Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.

Binocular Diplopia Caused by an Epiretinal Membrane With Foveal Displacement.

A 73-year-old woman presented with 3 years of monocular visual distortion and progressive binocular diplopia. She was found to have a comitant left hypertropia due to an epiretinal membrane causing inferior foveal drag. Displacement of the fovea from an epiretinal membrane is a likely under-recognized cause ocular cause of a comitant binocular diplopia.

Dog bite injuries of the eye and ocular adnexa.

Dog bites result in a diverse range of injuries and complications in the periocular region, particularly in school aged children. It is therefore incumbent on the oculoplastic surgeon to be well versed in both acute and long-term management. The intent of this review is to provide a systematic evaluation of the epidemiology, principles of dog bite wound care, and specific considerations related to common patterns of ophthalmic injury. Review of clinical literature from 1976 to 2014. The majority of periocular injuries result from seemingly benign interactions between young children and familiar dogs. Aggressive saline lavage combined with selective debridement of devitalized tissue is essential. High-risk wounds and vulnerable patient groups may benefit from preventive antibiotic coverage as well as appropriate rabies and tetanus prophylaxis. While the nuances of surgical repair are variable given the heterogeneity of presentation, systematic examination and an algorithm-driven approach underlie the optimal management of these complex injuries.

The DISCOVER Study 3-Year Results: Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery.

PURPOSE: To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. DESIGN: Prospective, consecutive case series. PARTICIPANTS: Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. METHODS: The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. MAIN OUTCOME MEASURES: Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. RESULTS: Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%-98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%-49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%-33.0%). CONCLUSIONS: The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

VOLUMETRIC SINGLE-LAYER INNER RETINAL ANALYSIS IN PATIENTS WITH HYDROXYCHLOROQUINE TOXICITY.

PURPOSE: To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes. METHODS: Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients. RESULTS: There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02). CONCLUSION: Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity.

Idiopathic Unilateral Enlargement of the Extraocular Muscles in an Infant.

A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis. A review of the literature reveals the exceptionally rare nature of this finding. While the authors cannot rule out an atypical case of congenital euthyroid eye disease, this constellation of findings is not consistent with thyroid eye disease and may represent previously described cases of idiopathic enlargement of the extraocular muscles.

Globe Loss From Intraocular Invasion of MIRAgel Scleral Buckle Components.

PURPOSE: To describe intraocular invasion of MIRAgel scleral buckles requiring evisceration. METHODS: This is an Institutional Review Board-approved retrospective consecutive case series of eyes requiring evisceration secondary to intraocular intrusion of MIRAgel implants performed at the Cole Eye Institute from 2000 to 2014. Charts were reviewed for age at surgery, gender, laterality, time between MIRAgel placement and evisceration, preoperative examination and imaging results, intraoperative findings, postoperative complications, and duration of follow up. RESULTS: Five eyes of 5 patients underwent evisceration due to a blind, painful eye secondary to MIRAgel expansion. The mean time between MIRAgel placement and evisceration was 21 years (range: 17-30 years). Preoperative ultrasound identified intraocular MIRAgel in 3 of 5 cases; however, intraocular MIRAgel was identified during surgery in all 5 cases. A transocular-approach orbitotomy was performed at the time of evisceration in an effort to remove the MIRAgel. Postoperative complications included ptosis and inability to retain an ocular prosthesis. No cases of orbital implant extrusion occurred. CONCLUSION: Scleral invasion and intraocular penetration of MIRAgel may occur decades after placement. This may result in a blind, painful eye requiring evisceration and orbitotomy to remove residual material. Suspicion of intraocular penetration of implant should be high in blind, painful eyes. Surgical removal can be difficult due to MIRAgel fragmentation. Conjunctival insufficiency may result in the need for further surgery after evisceration.

Transitional cell-type papillary carcinoma of the lacrimal sac manifesting as a medial canthal skin lesion.

A 61-year-old man presented with a 2.5 cm fungating skin lesion above the right medial canthus, accompanied by fluctuance and subtle inferotemporal globe displacement. The tumor had erupted 2 months previously and grown rapidly. Computed tomography (CT) revealed a 4.2 × 2.8 × 2.1 cm exophytic mass of the right orbit, superimposed on chronic dacryocystitis. Incisional biopsy disclosed faulty epithelial maturation sequence with possible basement membrane invasion. The patient underwent wide excision with medial maxillectomy, inferior turbinectomy, ethmoidectomy, and partial rhinectomy. The orbital floor was then reconstructed; a paramedian forehead flap and myocutaneous cheek advancement flap were used to fill cutaneous defects. All surgical margins were negative on both frozen and permanent sections. Definitive histopathology was consistent with transitional cell type papillary carcinoma of the lacrimal sac. Adjuvant radiotherapy was recommended, but the patient has declined further treatment. He remains recurrence-free at one year.

American Society of Retina Specialists Clinical Practice Guidelines on Multimodal Imaging for Retinal Disease.

Purpose: Advancements in retinal imaging have augmented our understanding of the pathology and structure-function relationships of retinal disease. No single diagnostic test is sufficient; rather, diagnostic and management strategies increasingly involve the synthesis of multiple imaging modalities. Methods: This literature review and editorial offer practical clinical guidelines for how the retina specialist can use multimodal imaging to manage retinal conditions. Results: Various imaging modalities offer information on different aspects of retinal structure and function. For example, optical coherence tomography (OCT) and B-scan ultrasonography can provide insights into the microstructural anatomy; fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography (OCTA) can reveal vascular integrity and perfusion status; and near-infrared reflectance and fundus autofluorescence (FAF) can characterize molecular components within tissues. Managing retinal vascular diseases often includes fundus photography, OCT, OCTA, and FA to evaluate for macular edema, retinal ischemia, and the secondary complications of neovascularization (NV). OCT and FAF play a key role in diagnosing and treating maculopathies. FA, OCTA, and ICGA can help identify macular NV, posterior uveitis, and choroidal venous insufficiency, which guides treatment strategies. Finally, OCT and B-scan ultrasonography can help with preoperative planning and prognostication in vitreoretinal surgical conditions. Conclusions: Today, the retina specialist has access to numerous retinal imaging modalities that can augment the clinical examination to help diagnose and manage retinal conditions. Understanding the capabilities and limitations of each modality is critical to maximizing its clinical utility.

Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Macrophage ß2 integrin-mediated, HuR-dependent stabilization of angiogenic factor-encoding mRNAs in inflammatory angiogenesis.

HuR is a member of the Drosophila Elav protein family that binds mRNA degradation sequences and prevents RNase-mediated degradation. Such HuR-mediated mRNA stabilization, which is stimulated by integrin engagement and is controlled at the level of HuR nuclear export, is critically involved in T-cell cytokine production. However, HuR's role in macrophage soluble factor production, in particular in response to angiogenic stimuli, has not yet been established. We show that the labile transcripts that encode vascular endothelial growth factor and matrix metalloproteinase-9 are stabilized when murine macrophages adhere to the ß(2) integrin ligand intercellular adhesion molecule-1. This mRNA stabilization response was absent in bone marrow-derived macrophages obtained from conditional macrophage-specific HuR knockout mice. The microvascular angiogenic response to an inflammatory stimulus (ie, subcutaneous polyvinyl alcohol sponge implantation) was markedly diminished in these macrophage HuR knockout mice despite the equal levels of macrophage localization to those observed in littermate wild-type controls. Furthermore, blood flow recovery and ischemic muscle neovascularization after femoral artery ligation were impaired in the conditional macrophage-specific HuR knockout mice. These results demonstrate that dynamic effects on mRNA, mediated by the RNA-binding and RNA-stabilizing protein HuR, are required for macrophage production of angiogenic factors, which play critical roles in the neovascular responses to a variety of stimuli, including tissue ischemia.

Retinal Findings and Cardiovascular Risk: Prognostic Conditions, Novel Biomarkers, and Emerging Image Analysis Techniques.

Many retinal diseases and imaging findings have pathophysiologic underpinnings in the function of the cardiovascular system. Myriad retinal conditions, new imaging biomarkers, and novel image analysis techniques have been investigated for their association with future cardiovascular risk or utility in cardiovascular risk prognostication. An intensive literature search was performed to identify relevant articles indexed in PubMed, Scopus, and Google Scholar for a targeted narrative review. This review investigates the literature on specific retinal disease states, such as retinal arterial and venous occlusions and cotton wool spots, that portend significantly increased risk of future cardiovascular events, such as stroke or myocardial infarction, and the implications for personalized patient counseling. Furthermore, conditions diagnosed primarily through retinal bioimaging, such as paracentral acute middle maculopathy and the newly discovered entity known as a retinal ischemic perivascular lesion, may be associated with future incident cardiovascular morbidity and are also discussed. As ever-more-sophisticated imaging biomarkers and analysis techniques are developed, the review concludes with a focused analysis of optical coherence tomography and optical coherence tomography angiography biomarkers under investigation for potential value in prognostication and personalized therapy in cardiovascular disease.

Anti-vascular endothelial growth factor dosing frequency and visual outcomes in macular oedema following branch retinal vein occlusion.

OBJECTIVES: To determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice. METHODS: Study eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year). RESULTS: Among 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (-3.0 vs 0.7 letters, respectively; p < 0.001). CONCLUSIONS: In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.