Scheimpflug-Based Tomographic Risk Factors for the Development of Acute Corneal Hydrops in Keratoconus.

PURPOSE: The purpose of this study was to assess the risk factors that predispose patients with keratoconus to develop acute corneal hydrops (ACH), including both clinical and tomographic risk factors. We additionally describe tomographic changes of the cornea over time after ACH. METHODS: We retrospectively reviewed patients with keratoconus who were followed at our institution from January 2015 to May 2023. Control eyes, defined as eyes with advanced keratoconus (stage IV Amsler-Krumeich classification on initial examination) were compared with eyes that developed ACH. Demographic, clinical, and tomographic factors were investigated. Visual acuity, keratometry, and corneal thickness were assessed at each follow-up visit to monitor progression over time. RESULTS: Twenty-three eyes of 19 patients developed ACH over the follow-up period. The incidence of known clinical associations including seasonal allergies, eye rubbing, snoring, asthma, and eczema was similar between the hydrops and control groups. There was a higher incidence of Down syndrome in the hydrops group ( P = 0.04). Eyes that developed hydrops had similar best corrected visual acuity on initial examination, but had steeper keratometry ( P = 0.003) and thinner corneas ( P < 0.001) than controls at baseline. After hydrops, progressive corneal flattening and reduced maximum keratometry occurred over time. However, final best corrected visual acuity was worse compared with initial examination before hydrops ( P = 0.03), as well as compared with control eyes ( P < 0.001). CONCLUSIONS: Risk factors of developing ACH include steep keratometry and thin corneas as well as Down syndrome. Although corneal flattening will occur after resolution of acute corneal edema, visual acuity worsened after ACH.

Spontaneous Reattachment of a Detached Sutured Descemet-Stripping Automated Endothelial Keratoplasty Graft.

Introduction: This is a case report of a spontaneous reattachment of Descemet-stripping automated endothelial keratoplasty (DSAEK). This graft was primarily sutured, and 20% sulfur hexafluoride (SF6) was injected into the anterior chamber, followed by graft detachment and spontaneous reattachment, 3 months later. Case Presentation: A 78-year-old male presented with DSAEK graft detachment, which was the patient's second DSAEK (the first also did not adhere). During the second surgery, the DSAEK graft was sutured and 20% SF6 was injected intraoperatively. Graft reattachment occurred without any intervention or repositioning 3 months after the 2nd DSAEK surgery. Conclusion: Spontaneous DSEAK late graft reattachment is possible, particularly in the setting of an anchoring suture. In some patients, waiting can be an option that can spare the patient the possible risks of graft repositioning, rebubbling, or repeating the DSAEK. Suturing the DSAEK graft primarily may have served as an anchor to keep the graft approximate and aid in attachment. A graft suture can be considered in the setting of a previously failed DSAEK due to DSAEK graft detachment.

Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Analysis of SARS-CoV-2 RNA on surfaces in New York City.

BACKGROUND: This study sought to determine the presence of SARS-CoV-2 virus on surfaces that trainees and faculty of an academic eye clinic came into contact with during daily life at the time of the COVID-19 pandemic in New York City. METHODS: This cross-sectional analysis involved collection of at least two samples by teams on four different days (November 9, 2020 - December 18, 2020) using sterile swabs (Puritan HydraFlock, Garden Grove, CA). Collection sites were grouped into four zones depending on proximity and amount of time personnel spent there. Samples were transported to the laboratory in transport medium and RNA was extracted using the QIAamp DSP Viral RNA Mini Kit (Qiagen, Germantown, MD). Presence of viral RNA was investigated using the Luna Universal Probe One-step RT-qPCR kit (New England Biolabs, Ipwsich, MA). RESULTS: 834 samples were submitted. Two were positive for SARS-CoV-2 RNA. The first was a sample from a patient bathroom sink handle in the main emergency department. The second was a nasal swab sample from a staff member who had been assigned to collect samples. Prior to this positive result, this asymptomatic staff member had tested positive for COVID-19, had quarantined for two weeks, and had received a negative test. CONCLUSION: Though COVID-19 is currently widespread in the United States, this study shows that health care personnel working in New York City at the Columbia University Irving Medical Center have a low chance of encountering viral RNA on surfaces they are in close contact with during daily life.

A case of infectious crystalline keratopathy after corneal cross-linking.

PURPOSE: To present a case of infectious crystalline keratopathy after corneal cross-linking in a child with delayed wound healing, and its successful management with antibiotic and anti-fungal eye drops. OBSERVATIONS: A 14-year-old male presented for a second opinion with a non-staining crystalline keratopathy after corneal crosslinking for progressive keratoconus. He reportedly rubbed his eyes vigorously in the post-operative course and had a slowly healing epithelial defect. He was treated with several antibiotic drops and was put on high dose topical difluprednate drops post-procedure for persistent corneal haze. His infection continued to progress until steroids were stopped and he was treated with topical voriconazole. While cultures were negative, the patient's visual acuity and corneal lesions improved significantly after starting voriconazole therapy and stopping steroid drops, pointing to a diagnosis of infectious crystalline keratopathy. CONCLUSIONS AND IMPORTANCE: This is one of the first case reports to describe a primary infectious crystalline keratopathy after a corneal cross-linking procedure, and the first to describe this phenomenon in a child with delayed corneal re-epithelialization. Though corneal cross-linking is a relatively safe procedure, atypical infections like crystalline keratopathy can occur in these patients in the setting of topical steroid use. Atypical organisms such as fungi should always be on the differential, especially for patients with recalcitrant infection in the setting of immunosuppression.

Chronic Early-Stage Ocular Cicatricial Pemphigoid.

Ocular cicatricial pemphigoid (OCP) represents an insidious, autoimmune-mediated disease of the conjunctiva, initially presenting as chronic conjunctivitis and progressing to fibrosis, cicatrization, and eventually blindness secondary to corneal keratinization. This series reports 3 cases presenting with chronic conjunctivitis lasting an average of 10 years without cicatrix formation, ultimately diagnosed as OCP based on direct immunofluorescence of conjunctival biopsy samples. This chronic conjunctivitis without fibrosis suggests the possibility of an OCP subtype with a prolonged early stage or prodrome prior to cicatrization, which may benefit from early diagnosis and treatment to prevent complications of this disease.

Prevalence and Risk Factors of Exposure Keratopathy Across Different Intensive Care Units.

PURPOSE: To determine the prevalence and risk factors of exposure keratopathy (EK) across different intensive care units (ICU) at Columbia University Medical Center, including the Pediatric ICU (PICU), Medical ICU (MICU), and Neurologic ICU (NICU). METHODS: In this prospective cohort study, 65 patients were examined daily during their admission in the PICU (27 patients), MICU (15 patients), and NICU (23 patients). Data on eyelid position, conjunctival and corneal changes, Bell's and blink reflexes, medications, Glasgow Coma Scale rating, and ventilation type were collected. RESULTS: Overall EK percentages were as follows: PICU 19%, MICU 60%, and NICU 48%. The prevalence of EK was lowest in the PICU (P = 0.013). Factors associated with EK were lagophthalmos (P < 0.001), an absent Bell's reflex (P = 0.003), an absent blink reflex (P < 0.001), conjunctival injection (P < 0.001), a low Glasgow Coma Scale score (P < 0.001), intubation (P < 0.001), surgery before examination (P < 0.001), dialysis (P = 0.002), and administration of opioid (P < 0.001), sedative (P < 0.001), and neuromuscular blocking medications (P = 0.006). CONCLUSIONS: This is the first study to examine the rates and risk factors of EK across different ICU settings. The prevalence of EK was lowest in the PICU, which may partly be explained by the increased number of PICU patients receiving noninvasive ventilation and the absence of conjunctival chemosis.

Using Anterior Segment Optical Coherence Tomography to Monitor Disease Progression in Peripheral Ulcerative Keratitis.

We report two cases of peripheral ulcerative keratitis (PUK) imaged with anterior segment optical coherence tomography (AS-OCT). The first patient had prolonged nonsteroidal anti-inflammatory drug use, while the second had inflammatory arthritis by laboratory findings without any systemic findings as well as possible concurrent tuberculosis. In both patients, AS-OCT demonstrated corneal thinning at the onset of the disease with improvement six months after initiation of intensive medical therapy. Our cases highlight the need for a multidisciplinary approach and careful monitoring in PUK cases, especially with objective measures such as corneal thickness assessed with AS-OCT.

Oxidative Stress-Related Molecular Biomarker Candidates for Glaucoma.

Purpose: Glaucoma-related molecular biomarkers can improve clinical testing to diagnose the disease early, predict its prognosis, and monitor treatment responses. Based on the evidence of increased oxidative stress in glaucomatous tissues, this study analyzed oxidative stress-related biomarker candidates in blood and aqueous humor samples with or without glaucoma. Methods: The blood and aqueous humor samples collected from carefully selected groups of 96 patients with glaucoma and 64 healthy subjects without glaucoma were included in the study. The samples were analyzed for protein carbonyls and advanced glycation end products (AGEs) through ELISA-based quantification assays. To allow proper comparisons, the Goldmann-Witmer coefficient that reflects the ratio of aqueous humor to blood values corrected to total protein concentration in individual samples was calculated. Results: Blood and aqueous humor levels of protein carbonyls and AGEs were found significantly higher in glaucomatous samples compared with age-matched nonglaucomatous controls (P < 0.001). The glaucoma-related increase in protein carbonyls and AGEs was more prominent in aqueous humor samples than blood samples (2.6-fold versus 1.9-fold for protein carbonyls, and 3.1-fold versus 1.9-fold for AGEs; P < 0.001). Comparison of the Goldmann-Witmer coefficients indicated greater values for protein carbonyls (1.37 ± 0.3 vs. 3.07 ± 0.8) and AGEs (1.2 ± 0.3 vs. 3.2 ± 1.1) in the glaucoma group (P < 0.001). Conclusions: Findings of this study encourage further validation studies of oxidative stress-related biomarkers in glaucoma. Analysis of protein carbonyls and AGEs in longitudinal studies of larger and heterogeneous patient cohorts should better assess the value of these promising candidates as molecular biomarkers of glaucoma for clinical predictions.

Pediatric corneal transplants.

PURPOSE OF REVIEW: Pediatric keratoplasty poses unique challenges in clinical and surgical management. However, successful transplantation can afford a child vision in an otherwise poorly seeing eye. This review will provide an update on recent advances in pediatric keratoplasty. RECENT FINDINGS: Although children who receive corneal transplants remain at increased risk of rejection, infection, and graft dehiscence compared with adult corneal transplant recipients, new surgical techniques, and advances in clinical management have led to better outcomes. Surgical modifications in penetrating keratoplasty (PKP) offer increased stabilization of the delicate pediatric eye. Lamellar surgery, including endothelial keratoplasty and deep anterior lamellar keratoplasty, can target specific diseased tissue in children with potentially fewer complications. The keratoprosthesis can be used successfully in children when the chance of success with PKP is especially low. SUMMARY: As our knowledge of prognostic indicators and surgical techniques continues to grow, we can offer children safer and more targeted surgeries for some of the most challenging corneal diseases. Ultimately, successful transplantation with long-term graft survival can be obtained by a multidisciplinary approach, with care across ophthalmic specialties, and a commitment to long-term follow-up by the patient's family.

Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus.

BACKGROUND/AIMS: Invasive fungal infections of the head and neck are rare life-threatening infections where prompt diagnosis and intervention is critical for survival. The aim of this study is to determine the clinical characteristics and outcomes of invasive fungal disease of the sinus and orbit, and to compare mucormycosis and Aspergillus infection. METHODS: A retrospective review was conducted from a single tertiary care eye and ear hospital over 20 years (1994-2014). Twenty-four patients with a confirmed pathological diagnosis of invasive fungal disease of the sinus and/or orbit were identified and their medical records were reviewed. The main outcome measures were type of fungus, location of disease, mortality and visual outcome. RESULTS: Patients with orbital involvement had a higher mortality and higher likelihood of mucormycosis infection compared with those with sinus-only disease (78.6% vs 20%, p=0.01; 86% vs 30%, p=0.01, respectively). Patients with mucormycosis had a higher mortality (71%) than patients with Aspergillus (29%); however, this was not statistically significant (p=0.16). All patients with orbital involvement and/or mucormycosis infections were immunosuppressed or had inadequately controlled diabetes, and had a cranial neuropathy or ocular motility dysfunction. All five post-transplant patients with orbital infections died, while the two transplant patients with sinus infections survived. CONCLUSIONS: Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus and have a higher mortality compared with infections sparing the orbit. History of transplant portends a dismal prognosis in orbital infections. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality.

New insights into the development of infantile intraocular medulloepithelioma.

PURPOSE: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas. DESIGN: Retrospective clinicohistopathologic and immunohistochemical study. METHODS: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins. RESULTS: Three infants (aged 1, 6, and 8 months) had iris neovascularization, 2 had anterior ciliary body tumors, and 1 a posterior tumor associated with a retinochoroidal coloboma. Each tumor displayed a premedullary monolayer of cuboidal epithelium that was S100(+), NeuN(-), and CRX(-) and that transitioned into a multilaminar medullary epithelium forming neurotubules with adluminal cells that were CRX(+). NeuN first appeared in ablumenal neurotubular cells in 1 tumor and was also discovered among neuroblast-appearing cells in another. The third tumor associated with a coloboma was CRX(-) and NeuN(-). CONCLUSIONS: A simple premedullary epithelial monolayer appears to be the fundamental source for the tumor and its multilaminar medullary epithelium. CRX(+) and NeuN(+) cells within the multilayered medullary layer approximate expression patterns similar to those found in retinal development and differentiation. Discovery of these biomarkers in the neoplastic ciliary epithelium in a small number of tumors indicates preliminarily that the most anterior layers of the optic cup have a retained retinal and neuroglial differentiation potentiality. The third case was CRX(-) and NeuN(-) and possibly arose from embryonic pigment epithelium at the edge of the retinochoroidal coloboma. These immunohistochemical findings offer histogenetic and potential diagnostic insights.

Intra-arterial chemotherapy for group C retinoblastoma with adjacent high-flow infantile hemangioma.

Intra-arterial chemotherapy for retinoblastoma is an emerging technique that is being adopted at various centers worldwide. The authors report the first case of an infantile hemangioma that shunted flow during intra-arterial chemotherapy in a 4-month-old girl who presented with macular group C retinoblastoma. Excellent tumor response was noted despite only a fraction of the dose entering the central retinal artery. Further studies to examine intra-arterial chemotherapy's pharmacokinetics and dose-response relations are warranted in order to minimize the necessary exposure to chemotherapy.

Functionally specific reorganization in human premotor cortex.

After unilateral stroke, the dorsal premotor cortex (PMd) in the intact hemisphere is often more active during movement of an affected limb. Whether this contributes to motor recovery is unclear. Functional magnetic resonance imaging (fMRI) was used to investigate short-term reorganization in right PMd after transcranial magnetic stimulation (TMS) disrupted the dominant left PMd, which is specialized for action selection. Even when 1 Hz left PMd TMS had no effect on behavior, there was a compensatory increase in activity in right PMd and connected medial premotor areas. This activity was specific to task periods of action selection as opposed to action execution. Compensatory activation changes were both functionally specific and anatomically specific: the same pattern was not seen after TMS of left sensorimotor cortex. Subsequent TMS of the reorganized right PMd did disrupt performance. Thus, this pattern of functional reorganization has a causal role in preserving behavior after neuronal challenge.

Ketamine produces lasting disruptions in encoding of sensory stimuli.

The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-D-aspartate hypofunction models of schizophrenia are discussed.