The Role of Optical Coherence Tomography Angiography in Glaucoma.

Glaucoma is the leading cause of irreversible vision loss and comprises a group of chronic optic neuropathies characterized by progressive retinal ganglion cell (RGC) loss. Various etiologies, including impaired blood supply to the optic nerve, have been implicated for glaucoma pathogenesis. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality for visualizing the ophthalmic microvasculature. Using blood flow as an intrinsic contrast agent, it distinguishes blood vessels from the surrounding tissue. Vessel density (VD) is mainly used as a metric for quantifying the ophthalmic microvasculature. The key anatomic regions for OCTA in glaucoma are the optic nerve head area including the peripapillary region, and the macular region. Specifically, VD of the superficial peripapillary and superficial macular microvasculature is reduced in glaucoma patients compared to unaffected subjects, and VD correlates with functional deficits measured by visual field (VF). This renders OCTA similar in diagnostic capabilities compared to structural retinal nerve fiber layer (RNFL) thickness measurements, especially in early glaucoma. Furthermore, in cases where RNFL thickness measurements are limited due to artifact or floor effect, OCTA technology can be used to evaluate and monitor glaucoma, such as in eyes with high myopia and eyes with advanced glaucoma. However, the clinical utility of OCTA in glaucoma management is limited due to the prevalence of imaging artifacts. Overall, OCTA can play a complementary role in structural OCT imaging and VF testing to aid in the diagnosis and monitoring of glaucoma.

HIV-1 subtypes and latent reservoirs.

PURPOSE OF REVIEW: We explore the current status of research on HIV-1 subtype-specific variations and their impact on HIV-1 latency. We also briefly address the controversy surrounding the decision-making process governing the ON/OFF states of HIV-1 transcription, specifically focusing on the regulatory elements, the long terminal repeat (LTR), and Tat. Understanding the decision-making process is crucial for developing effective intervention strategies, such as the 'shock-and-kill' approach, to reactivate latent HIV-1. RECENT FINDINGS: Attention has been drawn to subtype-specific transcription factor binding site (TFBS) variations and the possible impact of these variations on viral latency. Further, diverse subtype-specific assays have been developed to quantify the latent viral reservoirs. One interesting observation is the relatively larger latent reservoirs in HIV-1B infection than those of other viral subtypes, which needs rigorous validation. The emergence of LTR-variant viral strains in HIV-1C demonstrating significantly higher levels of latency reversal has been reported. SUMMARY: Despite persistent and substantial efforts, latent HIV-1 remains a formidable challenge to a functional cure. Determined and continued commitment is needed to understand the ON/OFF decision-making process of HIV-1 latency, develop rigorous assays for accurately quantifying the latent reservoirs, and identify potent latency-reversing agents and cocktails targeting multiple latency stages. The review emphasizes the importance of including diverse viral subtypes in future latency research.

Artifacts in OCT Retinal Nerve Fiber Layer Imaging in Patients with Boston Keratoprosthesis Type 1.

PURPOSE: To determine the clinical utility of OCT retinal nerve fiber layer (OCT RNFL) imaging for glaucoma evaluation in patients with Boston keratoprosthesis type 1 (KPro) by investigating imaging artifacts. DESIGN: Case-control study. SUBJECTS: Patients with KPro and without KPro (controls) matched for age, gender, and glaucoma diagnosis. METHODS: The most recent Cirrus OCT RNFL scan from 1 eye was categorized as having good signal strength (SS; ≥ 6 out of 10) or poor SS (< 6). Those with good SS were analyzed by 2 independent reviewers for artifacts. Images with good SS and no artifacts affecting the scanning circle were considered useful for glaucoma evaluation. MAIN OUTCOME MEASURES: The incidence of poor SS and artifacts in OCT RNFL images; patient characteristics associated with useful scans. RESULTS: Sixty-five patients with KPro and 75 controls were included; 89.2% of KPro patients and 89.3% of control subjects had glaucoma (P = 0.98). Forty percent of KPro patients and 5.3% of controls had poor SS (P < 0.001). The proportion of images with either poor SS or artifacts was similar in KPro (76.9%) vs. controls (72.0%, P = 0.51). The most common artifacts in both groups were missing data (43.6%, 53.2%, respectively, P = 0.32) and motion artifact (25.6%, 19.7%, respectively, P = 0.47). Images were useful for glaucoma evaluation in 43.1% of KPro patients and in 69.3% of controls (P = 0.002). In the KPro group, patients with useful OCT scans, compared with those without, had better visual acuity (0.4 ± 0.3 vs. 0.9 ± 0.7 logarithm of the minimum angle of resolution, P = 0.004), and did not have congenital corneal pathologies (0.0% vs. 24.3%, P = 0.008). A multivariate analysis showed that KPro patients with older age had higher odds of useful OCT images (odds ratio, 1.05; P = 0.03). Among KPro patients with useful OCT scans, retinal nerve fiber layer thickness correlated with observed cup-to-disc ratio (Pearson correlation: r = -0.42, P = 0.03). CONCLUSIONS: The rate of OCT RNFL images with either poor signal strength or artifacts in the KPro and control population was comparable. In patients with KPro, where intraocular pressure measurements are difficult and glaucoma is highly prevalent and often severe, OCT RNFL imaging can be useful for glaucoma evaluation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma.

Objective: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). Design: Cross-sectional case-control study. Subjects: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. Methods: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-ß1 (TGF-ß1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson's correlation (r) was used to assess correlations. Main Outcome Measures: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. Results: Patients with POAG (visual field mean deviation, -4.7 ± 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9% of POAG and 60.0% of control subjects had prior cataract surgery (P = 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 ± 7.9% vs. 2.6 ± 2.0%, P = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%, P < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2, P = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (P ≥ 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 ± 12.1 pg/ml vs. 10.0 ± 4.3 pg/ml; P < 0.001), but TGF-ß1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient r = -0.31, P = 0.03; r = -0.52, p = 0.002; r = -0.72, P < 0.001, respectively). Conclusions: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Combined Model of OCT Angiography and Structural OCT Parameters to Predict Paracentral Visual Field Loss in Primary Open-Angle Glaucoma.

PURPOSE: To assess a model combining OCT angiography (OCTA) and OCT parameters to predict the severity of paracentral visual field (VF) loss in primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: Forty-four patients with POAG and 42 control subjects underwent OCTA and OCT imaging with a swept-source OCT device. METHODS: The circumpapillary microvasculature was quantified for vessel density (cpVD) and flow (cpFlow) after delineation of Bruch's membrane opening and removal of large vessels. Retinal nerve fiber layer thickness (RNFLT) and Bruch's membrane opening-minimum rim width (BMO-MRW) were measured from structural OCT. Paracentral total deviation (PaTD) was defined as the average of the total deviation values within the central 10 degrees on Humphrey VF testing (24-2) for upper and lower hemifields. The OCT and OCTA parameters were measured in the affected hemisphere corresponding to the hemifield with lower PaTD for POAG patients. Models were created to predict affected PaTD based on RNFLT alone; RNFLT and BMO-MRW; OCTA alone; or RNFLT, BMO-MRW and OCTA parameters. The models were compared using coefficient of determination (r2) and Bayesian information criterion (BIC) score. Bayesian information criterion decrease of ≥6 indicates strong evidence for model improvement. MAIN OUTCOME MEASURES: Performance of models containing OCT and OCTA parameters in predicting PaTD. RESULTS: Patients with POAG and controls were similar in age and sex (65.9 ± 9.5 years and 38.4% male overall, P ≥ 0.56 for both). Average RNFLT, minimum RNFLT, average BMO-MRW, minimum BMO-MRW, cpVD, and cpFlow were all significantly lower (all P < 0.001) in the affected hemisphere in patients with POAG than in controls. In patients with POAG, the average mean deviation was -4.33 ± 3.25 dB; the PaTD of the affected hemifield averaged -4.55 ± 5.26 dB and correlated significantly with both OCTA and structural OCT parameters (r ≥ 0.43, P ≤ 0.004 for all). The model containing RNFLT, BMO-MRW, and OCTA parameters was superior in predicting affected PaTD (r2 = 0.47, BIC = 290.7), with higher r2 and lower BIC compared with all 3 other models. CONCLUSIONS: A combined model of OCTA and structural OCT parameters can predict the severity of paracentral VF loss of the affected hemifield, supporting clinical utility of OCTA in patients with POAG with paracentral VF loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Incidence and risk factors for glaucoma development and progression after corneal transplantation.

OBJECTIVE: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed. RESULTS: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0% and 17.8% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of ≥30 mmHg were each independently associated with glaucoma development or progression (p < 0.04 for all). CONCLUSIONS: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist.

Assessing Surface Shapes of the Optic Nerve Head and Peripapillary Retinal Nerve Fiber Layer in Glaucoma with Artificial Intelligence.

Purpose: To assess 3-dimensional surface shape patterns of the optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) in glaucoma with unsupervised artificial intelligence (AI). Design: Retrospective study. Participants: Patients with OCT scans obtained between 2016 and 2020 from Massachusetts Eye and Ear. Methods: The first reliable Cirrus (Carl Zeiss Meditec, Inc) ONH OCT scans from each eye were selected. The ONH and RNFL surface shape was represented by the vertical positions of the inner limiting membrane (ILM) relative to the lowest ILM vertical position in each eye. Nonnegative matrix factorization was applied to determine the ONH and RNFL surface shape patterns, which then were correlated with OCT and visual field (VF) loss parameters and subsequent VF loss rate. We tested whether using ONH and RNFL surface shape patterns improved the prediction accuracy for associated VF loss and subsequent VF loss rates measured by adjusted r 2 and Bayesian information criterion (BIC) difference compared with using established OCT parameters alone. Main Outcome Measures: Optic nerve head and RNFL surface shape patterns and prediction of the associated VF loss and subsequent VF loss rates. Results: We determined 14 ONH and RNFL surface shape patterns using 9854 OCT scans from 5912 participants. Worse mean deviation (MD) was most correlated (r = 0.29 and r = 0.24, Pearson correlation; each P < 0.001) with lower coefficients of patterns 10 and 12 representing inferior and superior para-ONH nerve thinning, respectively. Worse MD was associated most with higher coefficients of patterns 5, 4, and 9 (r = -0.16, r = -0.13, and r = -0.13, respectively), representing higher peripheral ONH and RNFL surfaces. In addition to established ONH summary parameters and 12-clock-hour RNFL thickness, using ONH and RNFL surface patterns improved (BIC decrease: 182, 144, and 101, respectively; BIC decrease ≥ 6; strong model improvement) the prediction of accompanied MD (r 2 from 0.32 to 0.37), superior (r 2 from 0.27 to 0.31), and inferior (r 2 from 0.17 to 0.21) paracentral loss and improved (BIC decrease: 8 and 8, respectively) the prediction of subsequent VF MD loss rates (r 2 from 0 to 0.13) and inferior paracentral loss rates (r 2 from 0 to 0.16). Conclusions: The ONH and RNFL surface shape patterns quantified by unsupervised AI techniques improved the structure-function relationship and subsequent VF loss rate prediction.

Glaucoma in Patients With Endothelial Keratoplasty.

ABSTRACT: Endothelial keratoplasty (EK), including Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, is now the most performed corneal transplant procedure in the United States. Intraocular pressure (IOP) elevation and glaucoma are common complications and can cause irreversible vision loss and corneal graft failure. This review will cover the incidence, risk factors, and management of glaucoma and IOP elevation after EK. Higher preoperative IOP, preoperative glaucoma, and certain indications for EK, such as bullous keratopathy, are associated with increased risk of glaucoma and glaucoma progression in patients undergoing EK. In addition, we summarize the studies assessing graft outcomes in EK patients with glaucoma or glaucoma surgery. Finally, we provide future directions to improve clinical care in EK patients with glaucoma.

Restoration of Vision in Severe, Cicatricial, Ocular Surface Disease With the Boston Keratoprosthesis Type II.

PURPOSE: To assess clinical outcomes of patients with severe, cicatricial ocular surface disease (OSD) implanted with the currently marketed design of the Boston keratoprosthesis type II (BK2). DESIGN: Retrospective cohort study. METHODS: Records of consecutive patients undergoing BK2 implantation from June 2009 to March 2021 were assessed for postoperative visual acuity, postoperative complications, device replacement, and additional surgeries. RESULTS: Fifty-six eyes of 53 patients with a mean follow-up of 45.8 months (range, 0.2-134.7 months) were included. Stevens-Johnson syndrome/toxic epidermal necrolysis was the most common indication (49.1%), followed by mucous membrane pemphigoid (39.6%) and other OSD (11.3%). Visual acuity improved from logMAR 2.2 ± 0.5 preoperatively to 1.5 ± 1.2 at final follow-up. Of 56 eyes, 50 saw ≥20/200 at some point postoperatively. Of the eyes with a follow-up of more than 5 years, 50.0% retained a visual acuity of ≥20/200 at their final follow-up. The most common complications over the entire postoperative course (mean ∼4 years) were de novo or worsening glaucoma (41.1%), choroidal effusions (30.3%), retinal detachment (25.0%), and end-stage glaucoma (25.0%). In a univariate analysis, patients who experienced irreversible loss of ≥20/200 visual acuity were more likely to have been previously implanted with an older design of BK2, less likely to be on preoperative systemic immunosuppressive therapy, and less likely to have undergone concurrent glaucoma tube implantation, compared to patients who retained ≥20/200 acuity (P < .04 for all). CONCLUSIONS: Advances in device design and postoperative care have made implantation of BK2 a viable option for corneal blindness in the setting of severe cicatricial OSD.

The Prevalence of Autoimmune Diseases in Patients with Primary Open-Angle Glaucoma Undergoing Ophthalmic Surgeries.

PURPOSE: To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. METHODS: All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. MAIN OUTCOME MEASURES: To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. RESULTS: A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27-5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P < 0.001). In a case-only analysis involving the eye with worse glaucoma, there was no statistical difference in visual field mean deviation or retinal nerve fiber layer (RNFL) thickness in POAG patients with AiD (n = 30) and without AiD (n = 142, P > 0.13, for both). CONCLUSIONS: A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.

Paired Optic Nerve Microvasculature and Nailfold Capillary Measurements in Primary Open-Angle Glaucoma.

Purpose: To assess microvascular beds in the optic nerve head (ONH), peripapillary tissue, and the nailfold in patients with primary open-angle glaucoma (POAG) versus controls. Methods: Patients with POAG (n = 22) and controls (n = 12) underwent swept-source optical coherence tomography angiography of ophthalmic microvasculature and nailfold video capillaroscopy of the hand. The main outcomes were vessel density (VD) and blood flow of the ONH, the peripapillary and the nailfold microvasculatures. Results: Patients with POAG were younger than controls (63.5 ± 9.4 vs. 69.9 ± 6.5 years, P = 0.03). Deep ONH VD and blood flow were lower in patients with POAG than controls (39.1% ± 3.5% vs. 43.8% ± 5.7%; 37.8% ± 5.3% vs. 46.0% ± 7.8%, respectively, P < 0.02 for both); similar results were observed with peripapillary VD (37.9 ± 2.6%, 43.4 ± 7.6%, respectively, P = 0.03). Nailfold capillary density and blood flow were lower in patients with POAG than controls (8.8 ± 1.0 vs. 9.8 ± 0.9 capillaries/mm; 19.9 ± 9.4 vs. 33.7 ± 9.8 pL/s, respectively; P < 0.009 for both). After adjusting for age and gender, deep ONH VD and blood flow, peripapillary VD, and nailfold capillary blood flow were lower in POAG than controls (ß = -0.04, -0.07, -0.05, -13.19, respectively, P ≤ 0.046 for all). Among all participants, there were positive correlations between deep ONH and nailfold capillary blood flow (Pearson's correlation coefficient r = 0.42, P = 0.02), peripapillary and nailfold capillary density (r = 0.43, P = 0.03), and peripapillary and nailfold capillary blood flow (r = 0.49, P = 0.01). Conclusions: Patients with POAG demonstrated morphologic and hemodynamic alterations in both ophthalmic and nailfold microvascular beds compared to controls. Translational Relevance: The concomitant abnormalities in nailfold capillaries and relevant ocular vascular beds in POAG suggest that the microvasculature may be a target for POAG treatment.

Ocular complications of perioperative anesthesia: a review.

Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.

Recent advances in the management of non-infectious posterior uveitis.

PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.

Window to the circulatory system: Ocular manifestations of cardiovascular diseases.

The changes in the cardiovascular system are associated with ocular manifestations, often as a consequence of pathological alteration in the ocular vasculature. The ease of visualization of these retinal changes makes the eye a window to the cardiovascular system. Certain congenital cardiac defects lead to changes in the retinal vascularity due to increased tortuosity and dilatation. In adults, the arterial dissection of internal carotid and vertebral arteries present as amaurosis fugax with or without oculo-sympathetic palsy. The patients with untreated infective endocarditis present with Roth spots, retinitis, embolic retinopathy, or sub-retinal abscesses. Hypoperfusive, hypertensive, or "mixed" retinopathy is a hallmark sign in patients of untreated infective endocarditis. Giant cell arteritis can present with ischemic ocular symptoms that may precipitate in irreversible vision loss. Systemic vascular manifestations such as coronary artery disease may manifest in a wide range of symptoms from amaurosis fugax to vision loss depending upon the size and location of retinal emboli. Rare cardio-oncological pathologies such as myxomas result in vision loss secondary to central retinal artery occlusion. A high clinical suspicion in patients with history of cardiovascular diseases can help in early diagnosis and management of impending, adverse cardiovascular and cerebrovascular events. In this review, we comprehensively discuss the spectrum of cardiac and vascular diseases with ocular manifestations as well as highlight the typical ocular presentations associated with these pathologies.

Semmelweis Reflex: An Age-Old Prejudice.

BACKGROUND: Semmelweis reflex is a human behavioral tendency to stick to preexisting beliefs and to reject fresh ideas that contradict them (despite adequate evidence). We aim to familiarize the readers with the term that not only has a significant historical background but also grave clinical implications. METHODS: A keyword search for "Semmelweis reflex," "Belief perseverance," "handwashing," and "Idea rejection" was conducted using PubMed Central, MEDLINE, and Google SCHOLAR. Literature published in paper-based journals and books was also searched. All manuscripts pertaining to these keywords were thoroughly analyzed for this review. RESULTS: The first section of our paper briefs the story of Ignaz Semmelweis and brushes on the contributions of other intellectual researchers that were rebuffed initially. The discussion further explains the root cause of this dismissal, an inherent bias against uncertainty that may be at the core of our fear for new ideas. Finally, this review explores the means by which we can prevent ourselves from being a victim of rejection. CONCLUSIONS: The age-old prejudice that is Semmelweis reflex is explored in this review. With careful and thorough study design, scientific rigor, and critical self-analysis of the manuscript, one can avoid being victimized by this reflex. The dual edged nature of this reflex lays unveiled when its importance is highlighted in the prematurely accepted medical failures. Understanding that any new idea goes through the grill of being critically analyzed and perceived encourages the scientist to hold on to the original thought as it may rather be practice changing.