A Novel Association Between Human Papillomavirus and Thyroid Eye Disease.

Context: Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R). Objective: To explore the potential involvement of viral infections in TED pathogenesis. Methods: Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, including Papillomaviridae , Paramyxoviridae , Herpesviridae , Enterovirus , Polyomaviridae , and Rhabdoviridae . Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed. Results: Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control ( M = 0.9387, SD = 0.3548), chronic TED ( M = 2.305, SD = 1.064), and active acute TED ( M = 4.087, SD = 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV. Conclusions: This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED's pathogenesis, opening new avenues for understanding and managing the disease.

Bilateral Thermal Keratopathy Due to Plasma Skin Regeneration.

A 40-year-old woman underwent periocular plasma skin regeneration, a cosmetic treatment for periorbital rejuvenation. She subsequently developed bilateral thermal keratitis, manifesting as blurred vision, irritation, and redness, with a vision decrease to 20/60 and 20/50 in her OD and OS, respectively. Examination demonstrated bilateral large, irregular corneal epithelial defects and edema, necessitating treatment with amniotic membrane grafts, bandage contact lenses, and hypertonic saline. One year posttreatment, her visual acuity improved to 20/20 and 20/25, albeit with ongoing symptomatic dryness and bilateral anterior stromal haze. This case, as only the second reported instance of ocular damage from periocular plasma skin regeneration, underscores the need for heightened awareness of potential ocular complications following plasma skin regeneration and reinforces the importance of protective measures during periocular procedures.

Beyond the Surface: A Systematic Review of Perforating and Penetrating Globe Injuries From Blepharoplasty.

PURPOSE: This study aims to address the infrequent but serious complication of globe injuries in blepharoplasty. METHODS: A case series of 3 patients with globe injuries postblepharoplasty is presented, along with a systematic literature review that revealed 13 previously reported cases. Quantitative and comparative analysis is described. RESULTS: Injuries ranged from deep thermal burns to full-thickness corneal or scleral lacerations, with one instance of traumatic cataract. The median time from surgery to symptom onset was 1 day, with a concerning median delay of 7 days to presentation to an ophthalmologist. Visual outcomes were generally poor, with nearly all patients experiencing permanent visual morbidity. The systematic review revealed 3 cases of endophthalmitis following perforating scleral injuries. Comparative analysis showed no significant differences in visual outcomes between penetrating and perforating injuries. CONCLUSIONS: The findings of this study emphasize the need for increased vigilance for globe injuries that require prompt ophthalmological evaluation following blepharoplasty, especially considering the observed delay in presentation and the extent of visual morbidity. The study advocates for improved practitioner training in recognizing and managing these complications and underscores the importance of patient education regarding the potential risks and the necessity of timely postoperative care.

Fundus imaging features of congenital rubella retinopathy.

PURPOSE: To evaluate the clinical characteristics of congenital rubella retinopathy (CRR) with modern fundus imaging. METHODS: Single-center case series. Eleven patients (2005-2020) at the Emory Eye Center with known or presumed CRR. Trained image readers reviewed fundus imaging (color fundus photography, widefield pseudocolor imaging, near-infrared reflectance imaging, autofluorescence imaging, and spectral-domain optical coherence tomography) for pre-specified features suggestive of CRR. RESULTS: Eleven patients with confirmed (63.6%) or presumed (36.3%) CRR were identified. All were female with median (range) age of 53 (35-67) years. Six (54.5%) were born during the 1964-1965 United States rubella epidemic. All had congenital hearing loss. Two (18.2%) had a congenital heart defect. Eleven (50.0%) eyes had salt-and-pepper retinal pigmentary changes. Twenty-two eyes (100.0%) had irregularly distributed regions of speckled hypoautofluorescence. One eye (4.5%) had a presumed macular neovascularization. CONCLUSION: Modern fundus imaging demonstrates characteristic features of CRR, even when pigmentary changes are not readily apparent on examination. Widefield autofluorescence findings of irregularly distributed speckled hypoautofluorescence are particularly revealing. This series of newly diagnosed adults with CRR may represent the milder end of the phenotypic spectrum of this condition, highlighting imaging findings that may aid in diagnostically challenging cases of CRR.

Colopathy Associated with Pentosan Polysulfate Use.

Introduction: We describe a novel colopathy associated with pentosan polysulfate (PPS) use and measure the strength of the drug-disease association. Methods: Two-part investigation. In the cohort study of individuals with a history of prior long-term PPS use, case histories were obtained and gastrointestinal disease course was followed with review of endoscopy records and histopathology specimens. Findings were summarized with descriptive statistics. In the cross-sectional study of individuals with interstitial cystitis, drug exposure and medical histories were obtained for patients seen at a single clinical center. Strength of association between PPS use and diagnoses of inflammatory bowel disease (IBD) and/or irritable bowel syndrome (IBS) was measured with multivariate logistic regression. Results: In the cohort study of 13 participants, median PPS exposure was 2.04 kg (0.99-2.54). Eleven (84.6%) developed symptoms suggestive of IBD and/or IBS after initiation of PPS therapy. Of the 10 participants whose endoscopic and histopathologic findings we reviewed, six had abnormal-appearing colonic mucosa on endoscopy and all 10 had abnormal mucosal changes on histology. Clinical and histologic improvement was observed after PPS cessation. In the cross-sectional study of 219 subjects with interstitial cystitis, PPS use was a statistically significant predictor of both the IBD [adjusted odds ratio=3.3 (95% confidence interval, 1.2-8.8, p=0.02)] and the composite IBD+IBS [adjusted odds ratio=3.3 (95% confidence interval, 1.5-7.3, p=0.002)] outcomes. Discussion: We describe a strong association between PPS use and a clinical diagnosis of IBD and/or IBS. Histopathologic findings suggest a novel drug-associated colopathy, with some subjects requiring colectomy for dysplasia.

Multidrug-Resistant Pseudomonas aeruginosa Keratitis Associated With Artificial Tear Use.

This case report describes severe multidrug-resistant Pseudomonas aeruginosa keratitis in a 72-year-old man after EzriCare artificial tear use.

Presumptive Idiopathic Intracranial Hypertension Based on Neuroimaging Findings: A Referral Pattern Study.

BACKGROUND: Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis. METHODS: Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for "papilledema"; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist. RESULTS: Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for "papilledema." Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema. CONCLUSIONS: One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these "rule-out IIH" consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US.

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion.

OBJECTIVES: Diffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. MATERIALS AND METHODS: Retrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. RESULTS: We included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). CONCLUSIONS: In this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.

PROLIFERATIVE RETINOPATHY IN A 13-YEAR-OLD WITH ADAMS-OLIVER SYNDROME.

PURPOSE: Adams-Oliver syndrome is a rare, inherited disorder of embryologic development that affects multiple systems. Ocular manifestations have been poorly characterized because of the low prevalence and high mortality of the disease when it is associated with internal organ and/or ophthalmic manifestations. We present a case of Adams-Oliver syndrome in a 13-year-old patient whose multimodal retinal imaging findings helped direct management. METHODS: Single patient case report reviewing medical records and imaging. RESULTS: Visual acuity upon presentation was 20/40 in each eye. Ultra-widefield fluorescein angiography revealed peripheral nonperfusion with terminal vascular bulbs, and leakage from a temporal fibrovascular complex in the left eye. Fundus autofluorescence imaging showed hyperautofluorescence associated with optic disc drusen and the fibrovascular complex. Treatment with targeted laser photocoagulation was associated with regression of the neovascularization. CONCLUSION: Retinal manifestations of Adams-Oliver syndrome as observed with ultra-widefield fundus imaging may resemble those of familial exudative vitreoretinopathy and retinopathy of prematurity. Treatment of avascular retina with panretinal photocoagulation can be considered.

Referral Patterns of Central Retinal Artery Occlusion to an Academic Center Affiliated With a Stroke Center.

BACKGROUND: Central retinal artery occlusion (CRAO) is a medical emergency, and patients who present acutely should be immediately referred to the nearest stroke center. We evaluated practice patterns for CRAO management at one academic center over the last decade. METHODS: This was a retrospective study on all adult patients diagnosed with a CRAO seen at one tertiary hospital and outpatient clinic affiliated with a comprehensive stroke center ("our institution") from 2010 to 2020. Our electronic medical records were searched for CRAO diagnoses, and patient medical records were reviewed. The exclusion criteria were incorrect diagnosis, unclear diagnosis, historical CRAO, or satellite clinic location. Demographics, distance and time to presentation to our institution, number and type of prior providers seen, diagnostic tests performed, and treatments provided were collected. Summary statistics of median, mean, and frequency were calculated and reported with measures of variance (interquartile range [IQR], ranges). F, Tukey, and Fisher exact tests were used for comparisons. RESULTS: We included 181 patients with a diagnosis of CRAO (80 [44.2%] women; median age 69 years [range 20-101]). The median distance from patient's home to our institution was 27.8 miles (IQR 15.5-57.4; range 2.4-930). The median time from visual loss to presentation at our institution was 144 hours (IQR 23-442 hours, range 0.5-2,920) from 2010 to 2013, 72 hours (IQR 10.5-372 hours, range 0-13,140) from 2014 to 2016, and 48 hours (IQR 7-180 hours, range 0-8,030) from 2017 to 2020 (P = 0.07). 91/181 (50%) patients presented to an outpatient provider. 73/181 (40%) presented to an emergency department. Eighty-six percent presented within 1 week of visual loss onset, and rates of comprehensive inpatient evaluation for acute CRAO improved from 44% in 2010-2013 to 82% in 2017-2020 (P < 0.01). CONCLUSIONS: Patients with CRAO often present late and only after evaluation by multiple outpatient providers. Improvement has occurred over the past decade, but delays underscore the barriers to performing clinical trials evaluating very acute treatments for CRAO. Educational interventions for healthcare providers and patients are necessary.

Acute Central Retinal Artery Occlusion Seen within 24 Hours at a Tertiary Institution.

OBJECTIVE: Acute central retinal artery occlusion (CRAO) is an emergency with poor visual outcome. Intravenous thrombolysis within 4.5 h of vision loss is safe and may improve vision, but is rarely administered because of frequent delays in presentation. We describe a subgroup of CRAO patients presenting within 24 h of vision loss to a tertiary care center affiliated with a comprehensive stroke center. MATERIALS AND METHODS: Retrospective review of 181 consecutive CRAO patients seen at our institution from 2010 to 2020. RESULTS: Out of 181 CRAO patients, 62 (34%) presented within 24 h of vision loss and tended to live closer to the hospital. These patients were more likely to be admitted to the hospital and receive comprehensive stroke work-up compared to patients who presented after 24 h of vision loss. Patients presenting after 24 h did not necessarily receive prior appropriate work-up at outside institutions. Conservative treatments for CRAO were administered to 20/181 patients, and only 3 patients received intravenous thrombolysis. CONCLUSIONS: Patients with CRAO do not present to the emergency department fast enough and diagnosis of CRAO is often delayed. Despite having a protocol in place, only 3/181 patients received IV thrombolysis, emphasizing the difficulty in administering very acute treatments for CRAO. Public education regarding CRAO is necessary to improve presentation times, management, and visual outcomes. Hospitals need to develop accelerated diagnostic pathway protocols for patients with acute vision loss so that CRAO patients may be diagnosed and be considered for potential acute treatments as quickly as possible.

Prevalence of Incidentally Detected Signs of Intracranial Hypertension on Magnetic Resonance Imaging and Their Association With Papilledema.

Importance: Magnetic resonance imaging (MRI) signs of intracranial hypertension (IH) are traditionally associated with idiopathic intracranial hypertension (IIH), but these signs are also detected among individuals with primary headaches and among asymptomatic individuals without papilledema. Objective: To examine the prevalence of MRI signs of IH among consecutive outpatients undergoing brain MRI for any clinical indication and to explore their association with papilledema. Design, Setting, and Participants: This prospective cross-sectional study of outpatients undergoing brain MRI at 1 outpatient imaging facility was conducted between August 1, 2019, and March 31, 2020, with ocular fundus photographs taken concurrently. Radiographic images from consecutive adult patients who were undergoing brain MRI and able to participate in fundus photography were analyzed for MRI signs of IH. A univariate analysis using either Fisher exact tests or t tests was performed. Main Outcomes and Measures: Prevalence of MRI signs of IH and prevalence of papilledema detected on ocular fundus photographs. Radiographic signs of IH included empty sella, optic nerve head protrusion, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, enlarged Meckel caves, cephaloceles, cerebellar tonsillar descent, and bilateral transverse venous sinus stenosis. Results: A total of 388 patients were screened for eligibility; of those, 92 patients were excluded (58 declined participation, 16 were unable to consent, 14 were unable to complete fundus photography, and 4 completed MRI and fundus photography twice, so their second set of findings was removed). Among the 296 patients included in the study, the median age was 49.5 years (interquartile range, 37.8-62.0 years), and 188 patients (63.5%) were female. The most common indication for MRI was surveillance of a brain neoplasm (82 patients [27.7%]). Investigations of headaches (26 patients [8.8%]) and disorders of intracranial pressure (4 patients [1.4%]) were uncommon. At least 1 radiographic sign of IH was present in 145 patients (49.0%). Among 296 total study patients, 98 patients (33.1%) had empty sella, 47 patients (15.9%) had enlarged Meckel caves, 32 patients (10.8%) had increased perioptic cerebrospinal fluid, 23 patients (7.8%) had optic nerve tortuosity, 2 patients (0.7%) had scleral flattening, and 4 patients (1.4%) had cephaloceles. Bilateral transverse venous sinus stenosis was present in 6 of 198 patients (3.0%). Five patients (1.7%) had papilledema. Compared with patients without papilledema, those with papilledema had a significantly higher body mass index and history of IIH, in addition to an increased prevalence of empty sella, optic nerve tortuosity, and transverse venous sinus stenosis detected on MRI. The prevalence of papilledema increased from 2.8% among patients with at least 1 MRI sign of IH to 40.0% among patients with 4 or more MRI signs of IH. Conclusions and Relevance: Magnetic resonance imaging signs of IH were common among patients undergoing brain MRI in this study but rarely associated with papilledema. The management of patients with incidentally detected signs of IH likely does not require systematic lumbar puncture unless concerning symptoms or papilledema are present.

Homonymous thinning on macular optical coherence tomography indicating retrograde trans-synaptic degeneration from occipital infarctions.

Inner retinal thinning on optical coherence tomography (OCT) occurring through retrograde trans-synaptic degeneration is an increasingly recognized phenomenon, even in acquired retro-chiasmal brain lesions. We describe a man with stable visual field defects from multiple bilateral posterior circulation infarctions, who had ganglion cell complex (GCC) thinning on macular OCT that corresponded precisely with his visual field defects. In contrast to previous reports indicating that peripapillary retinal nerve fiber layer (RNFL) changes are important in detecting this phenomenon, the peripapillary RFNL thickness and the optic disc appearance of our patient were relatively unaffected. Our case contributes to the growing body of evidence that retrograde trans-synaptic degeneration can manifest as isolated macular OCT findings.

Patient Perceptions of SARS-CoV-2 Exposure Risk and Association With Continuity of Ophthalmic Care.

Importance: Patient perceptions regarding the risks of obtaining in-person ophthalmic care during the coronavirus disease 2019 (COVID-19) pandemic may affect adherence to recommended treatment plans and influence visual outcomes. A deeper understanding of patient perspectives will inform strategies to optimize adherence with vision-preserving therapies. Objective: To evaluate perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care. Design, Setting, and Participants: This survey study included a nonvalidated telephone survey designed in April and May of 2020 and a retrospective medical record review conducted in parallel with survey administration from May 22 to August 18, 2020. Participants were recruited from 2 tertiary eye care centers (Emory Eye Center in Atlanta, Georgia, and W.K. Kellogg Eye Center in Ann Arbor, Michigan). The study included a random sample of patients with diagnoses of exudative age-related macular degeneration (AMD) or diabetic retinopathy (DR) who received an intravitreal injection between January 6 and March 13, 2020, and were scheduled for a second injection between March 13 and May 6, 2020. Main Outcomes and Measures: Association between perceptions regarding COVID-19 risks and loss to follow-up. Results: Of 1004 eligible patients, 423 (42%) were successfully contacted, and 348 (82%) agreed to participate (participants' mean [SD] age, 75 [12] years; 195 women [56%]; 287 White [82%] patients). Respondents had a mean (SD) of 2.7 (1.1) comorbidities associated with severe COVID-19, and 77 (22%) knew someone with COVID-19. Of all respondents, 163 (47%) were very concerned or moderately concerned about vision loss from missed treatments during the pandemic. Although 208 (60%) believed the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exposure at the eye clinic was extremely unlikely or unlikely, 49 (14%) believed it was extremely likely or likely. Seventy-eight participants (22%) were lost to follow-up. Concern regarding COVID-19 exposure during clinic visits (odds ratio [OR], 3.9; 95% CI, 1.8-8.4) and diagnosis of DR (vs AMD) (OR, 8.130; 95% CI, 3.367-20.408) were associated with an increase in likelihood of loss to follow-up. Conclusions and Relevance: Among patients at high risk for vision loss from lapses in care, many expressed concerns regarding the effect of the pandemic on their ability to receive timely care. Survey results suggest that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up. These results support the potential importance of clearly conveying infection-control measures.

Outcomes of Infectious Endophthalmitis in Patients with Systemic Antibiotic Allergies to Penicillins, Cephalosporins, or Vancomycin.

PURPOSE: The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration. DESIGN: Single-center, retrospective cohort study. PARTICIPANTS: All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit. RESULTS: Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection. CONCLUSIONS: There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use.

A Functional Non-coding RNA Is Produced from xbp-1 mRNA.

The xbp-1 mRNA encodes the XBP-1 transcription factor, a critical part of the unfolded protein response. Here we report that an RNA fragment produced from xbp-1 mRNA cleavage is a biologically active non-coding RNA (ncRNA) essential for axon regeneration in Caenorhabditis elegans. We show that the xbp-1 ncRNA acts independently of the protein-coding function of the xbp-1 transcript as part of a dual output xbp-1 mRNA stress response axis. Structural analysis indicates that the function of the xbp-1 ncRNA depends on a single RNA stem; this stem forms only in the cleaved xbp-1 ncRNA fragment. Disruption of this stem abolishes the non-coding, but not the coding, function of the endogenous xbp-1 transcript. Thus, cleavage of the xbp-1 mRNA bifurcates it into a coding and a non-coding pathway; modulation of the two pathways may allow neurons to fine-tune their response to injury and other stresses.

Conditional survival analysis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with an approximate 5-year survival of greater than 50% in patients after surgical resection. Survival estimates have limited utility for patients who have survived several years after initial treatment. We analyzed how conditional survival (CS) after curative-intent surgery for HCC predicts survival estimates over time. METHODS: NCDB (2004-2014) was queried for patients undergoing definitive surgical resection for HCC. Cumulative overall survival (OS) was calculated using the Kaplan-Meier method, and CS at x years after diagnosis was calculated as CS1 = OS (X+5) /OS(X) . RESULTS: The final analysis encompassed 11 357 patients. Age, negative margin status, grade severity and radiation before surgery were statistically significant predictors of cumulative overall conditional survival (P ≤ .0001). Overall unconditional 5-year survival was 65.7%, but CS estimates were higher. A patient who has already survived 3 years has an additional 2-year, or 5-year CS, estimate of 86.96%. CONCLUSION: Survival estimates following hepatic resection in HCC patients change according to survival time accrued since surgery. CS estimates are improved relative to unconditional OS. The impact of different variables influencing OS is likewise nonlinear over the course of time after surgery.

Optimal timing and treatment strategy for pancreatic cancer.

BACKGROUND: For pancreatic adenocarcinoma (PDAC), no studies have established any association between earlier treatment initiation and long-term outcomes. In addition, an optimal type of initial treatment for the localized disease remains ill-defined. METHODS: Patients in the National Cancer Database (2004-2015) with clinical stage I (CS-I) and II (CS-II) PDAC who underwent curative-intent resection were included. Optimal time from diagnosis-to-treatment including neoadjuvant chemotherapy, neoadjuvant chemoradiation, or upfront surgery was assessed. An optimal type of treatment was evaluated. The primary outcome was overall survival (OS). RESULTS: Among 29 167 patients, starting any treatment within 0 to 6 weeks was associated with improved median OS compared with 7 to 12 weeks (21.0 vs 20.1 months; P = .004). This persisted when accounting for sex, race, and Charlson-Deyo score (hazard ratio [HR], 0.94; P = 0.02) and on subset analysis for CS-I (23.5 vs 21.8 months; P = .04) and CS-II (19.4 vs 18.3 months; P = .03). Neoadjuvant chemotherapy was associated with improved OS compared with neoadjuvant chemoradiation (25.6 vs 22.7 months; P < .0001) or US (25.6 vs 20.1 months; P < .0001) even when accounting for sex, race, and Charlson-Deyo score (neoadjuvant chemoradiation: HR, 0.86; P < .001; US: HR, 0.79; P < .001). This improvement persisted in subset analysis with NC compared with neoadjuvant chemoradiation (CS-I: 28.6 vs 25.0 months; CS-II: 25.0 vs 22.9 months; both P < .0001) and to US (CS-I: 28.6 vs 22.9 months; CS-II: 24.7 vs 18.4 months; both P < .0001). On multivariable analysis for each CS-I/CS-II, NC remained associated with 20% improved survival compared with neoadjuvant chemoradiation or upfront surgery. CONCLUSIONS: For PDAC, initiation of therapy within 6 weeks from diagnosis is associated with improved survival, with neoadjuvant chemotherapy associated with the best survival compared with neoadjuvant chemoradiation or upfront surgery.

Should adenosquamous esophageal cancer be treated like adenocarcinoma or squamous cell carcinoma?

BACKGROUND: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct outcomes, treatment strategies, and response profiles to therapy. Adenosquamous carcinoma (ASC) is thought to behave more aggressively than each of its counterparts. The aim of this study is to determine ifASC is best managed as AC or SCC. METHODS: National Cancer Database (2004-2015) was queried for patients with nonmetastatic esophageal ASC. The analysis was stratified by clinical node-negative (cN0) or clinical node-positive (cN1-3). Treatment was categorized into chemoradiation alone, surgery alone, or preoperative chemoradiation followed by surgery. The primary outcome was 5-year overall survival (OS). RESULTS: Among 352 patients, 43% were cN0 (n = 151), 57% were cN1-3 (n = 201) and 55% had chemoradiation alone (n = 194), 15% surgery alone (n = 53), and 30% preoperative chemoradiation (n = 105). Among patients who had preoperative chemoradiation, 20% had pathologic complete response (n = 17). For either cN0 or cN1-3, Charlson-Deyo Comorbidity Index did not differ among the treatment groups(all p > 0.05). On Kaplan-Meier analysis for cN0, treatment with surgery alone had comparable OS to preoperative chemoradiation (47% vs 34%; P = .5) and each had improved OS compared to chemoradiation alone (30%; P = .02; P = .06). On univariate analysis for cN0, clinical T category was not associated with OS. For cN1-3, however, preoperative chemoradiation was associated with improved OS when compared to chemoradiation alone or surgery alone (27% vs 19% vs 0%; P < .001). This persisted when accounting for age and clinical T category (hazard ratio: 0.45; P < .001). CONCLUSION: Esophageal ASC behaves more like AC in response to chemoradiation and survival based on treatment modality. A complete response to chemoradiation is only 20% unlike what has been shown for SCC, where chemoradiation is an acceptable definitive therapy. Esophageal ASC should be managed more like AC.