Topographic Measurement of the Subretinal Pigment Epithelium Space in Normal Aging and Age-Related Macular Degeneration Using High-Resolution OCT.

Purpose: A micrometer scale hyporeflective band within the retinal pigment epithelium basal lamina - Bruch's membrane complex (RPE-BL-BrM) was topographically measured in aging and age-related macular degeneration (AMD). Methods: In a prospective cross-sectional study, 90 normal eyes from 76 subjects (range = 23-90 years) and 53 dry AMD eyes from 47 subjects (range = 62-91 years) were enrolled. Isotropic volume raster scans over 6 mm × 6 mm (500 × 500 A-scans) were acquired using a high-resolution (2.7 µm axial resolution) spectral-domain optical coherence tomography (SD-OCT) prototype instrument. Six consecutive optical coherence tomography (OCT) volumes were computationally motion-corrected and fused to improve feature visibility. A boundary regression neural network was developed to measure hyporeflective band thickness. Topographic dependence was evaluated over a 6-mm-diameter Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Results: The hyporeflective band thickness map (median of 4.3 µm and 7.8 µm in normal and AMD eyes, respectively) is thicker below and radially symmetric around the fovea. In normal eyes, age-associated differences occur within 0.7 to 2.3 mm from the foveal center (P < 0.05). In AMD eyes, the hyporeflective band is hypothesized to be basal laminar deposits (BLamDs) and is thicker within the 3-mm ETDRS circle (P < 0.0002) compared with normal eyes. The inner ring is the most sensitive location to detect age versus AMD-associated changes within the RPE-BL-BrM. AMD eyes with subretinal drusenoid deposits (SDDs) have a significantly thicker hyporeflective band (P < 0.001) than those without SDDs. Conclusions: The hyporeflective band is a quantifiable biomarker which differentiates AMD from aging. Longitudinal studies are warranted. The hyporeflective band may be a useful biomarker for risk stratification and disease progression.

Multimodal imaging in deferasirox-mediated retinopathy.

INTRODUCTION: Deferasirox is the only iron chelator available in oral formulation and a rare cause of pigmentary retinopathy. We report the first case of multimodal imaging in an adult with deferasirox retinopathy. METHODS: Case report and literature review, with search terms including deferasirox retinopathy and deferasirox toxicity. RESULTS: A 63-year-old man with end stage renal disease and transfusion-dependent anemia on deferasirox for one year presented with asymptomatic pigment epitheliopathy. Optical coherence tomography featured outer retinal and retinal pigment epithelial discontinuity corresponding to hypoautofluorescence on fundus autofluorescence and blocking on fluorescein angiography. Multifocal electroretinography revealed subtle reduction in all amplitudes. CONCLUSIONS: Retinal examinations should be considered for patients requiring chronic administration of deferasirox.

The Big Data Gap: Asymmetric Information in the Ophthalmology Residency Match Process and the Argument for Transparent Residency Data.

Background The ophthalmology match is an important step for graduating medical students that defines their future career. Residency programs demonstrate significant variability due to differences in size, location, research output, subspecialty exposure, surgical case load, and alumni fellowship/practice placement. Despite the importance of informed decision-making, applicants often find limited, inconsistent information about potential programs. Purpose The purpose of this study was to characterize and identify gaps in the information available to residents in the 2022 to 2023 Match. Methods The SFMatch Web site was reviewed to identify programs included as well as characteristics cited on each program's webpage. Program webpages were used to evaluate availability and consistency of data on site surgical caseload, fellowship slots, and teaching staff. Results Of the 121 programs included on SFMatch, 23 (19%) provided no data on August 15, 2022 (15 days prior to application submission deadline) and 9 (7%) lacked program data on October 15, 2022. Though most programs provided mean cataract volume, data on volume of other procedures for graduating residents was highly variable and occasionally misleading. Programs did not provide information on several academic and social considerations that may influence match ranking choice. Conclusion Applicants often must read "between the lines" to identify residency program strengths and weaknesses. Data crucial to informing the application process remain sparse, unavailable, or spread across resources. Limited data increases applicant dependence on word-of-mouth knowledge to inform decision-making. This might reduce diversity by limiting successful applicants to those with existing connections within the field.

Erratum: The Big Data Gap: Asymmetric Information in the Ophthalmology Residency Match Process and the Argument for Transparent Residency Data.

[This corrects the article DOI: 10.1055/s-0043-1777413.].

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN PREGNANCY.

PURPOSE: To describe a case of paracentral acute middle maculopathy (PAMM) during the first trimester of pregnancy without other ocular or systemic comorbidities. METHODS: Case report. RESULTS: A 31-year-old woman in her first trimester of pregnancy presented with a paracentral scotoma in the absence of other retinal pathology or systemic associations. Optical coherence tomography showed a classic acute PAMM lesion, and optical coherence tomography angiography showed preservation of vascular flow in the area of the PAMM lesion 1 week after symptom onset. Subsequent workup for underlying systemic disease that can affect the retinal vasculature was negative. CONCLUSION: Paracentral acute middle maculopathy lesions have been described in eyes with retinal vascular disease and in people with systemic vascular diseases or events. This is the first described case of a PAMM lesion in the absence of associated factors other than an uncomplicated pregnancy.

Anabolic Steroid Use for Weight and Strength Gain in Critically Ill Patients: A Case Series and Review of the Literature.

BACKGROUND: An important long-term complication of critical illness is significant weakness and its resulting functional impairment. Recent advances have aimed to prevent critical illness weakness via early mobilisation of patients, minimising sedation, and optimising nutrition. One other potential treatment may be to provide anabolic support in the recovery phase, especially as patients have decreased levels of anabolic hormones. CASE PRESENTATION: We describe a case series of 4 patients who had either (1) profound critical illness myopathy and (2) profound weight loss. All patients were already receiving appropriate nutritional support and physiotherapy. All patients had functional improvements in their muscle strength. CONCLUSIONS: For patients in the recovery phase of critical illness, we provide examples of when anabolic steroid supplementation may assist the treating clinicians in rehabilitating their patients who are still in the Intensive Care Unit. We discuss patient selection and the current supporting literature for anabolic supplementation in critically ill patients.

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 108 vector genomes (vg); cohort 2, 2 × 109 vg; cohort 3, 6 × 109 vg; and cohort 4, 2 × 1010 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 1010 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. FINDINGS: 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 1010 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 1010 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to a mean of 53·2 ng/mL at week 52 (SD 17·1). At baseline, four of these five patients were negative for anti-AAV2 serum antibodies and the fifth had a very low titre (1:100) of anti-AAV2 antibodies, whereas four of the five non-expressers of sFLT01 had titres of 1:400 or greater. In 11 of 19 patients with intraretinal or subretinal fluid at baseline judged to be reversible, six showed substantial fluid reduction and improvement in vision, whereas five showed no fluid reduction. One patient in cohort 5 showed a large decrease in vision between weeks 26 and 52 that was not thought to be vector-related. INTERPRETATION: Intravitreous injection of AAV2-sFLT01 seemed to be safe and well tolerated at all doses. Additional studies are needed to identify sources of variability in expression and anti-permeability activity, including the potential effect of baseline anti-AAV2 serum antibodies. FUNDING: Sanofi Genzyme, Framingham, MA, USA.

Morbidity in Pregnant Women Associated with Unverified Penicillin Allergies, Antibiotic Use, and Group B Streptococcus Infections.

CONTEXT: The morbidity potentially associated with unverified penicillin allergy in pregnant women, with and without group B streptococcus (GBS) infections, is unknown. Penicillin allergy testing is safe during pregnancy but is done infrequently. OBJECTIVE: To determine morbidity associated with antibiotic use in a large cohort of pregnant women, with and without an unverified history of penicillin allergy, and with and without GBS. DESIGN: Retrospective. All pregnant women who delivered live infants in Kaiser Permanente Southern California between January 1, 2009, and December 31, 2014, were identified. MAIN OUTCOME MEASURES: Penicillin allergy status at delivery, delivery method, maternal and infant hospital utilization, peripartum antibiotic exposures, new antibiotic-associated adverse drug reactions, and new Clostridium difficile infections. RESULTS: There were 170,379 unique women who had 201,316 pregnancies during the study period. There were 16,084 pregnancies in women with an active, but unverified, penicillin allergy at delivery. There were 42,524 pregnancies in GBS-positive women, and 3500 also had a penicillin allergy. Women with a penicillin allergy, with or without GBS, had significantly (about 10%) higher cesarean section rates and spent significantly more (about 0.1) days in the hospital after delivery. Among GBS-positive women, those with an unverified penicillin allergy were exposed to significantly more cefazolin, clindamycin, vancomycin, and gentamicin and had significantly higher rates of adverse drug reactions associated with all antibiotic use. CONCLUSIONS: Unverified penicillin allergy is associated with more hospital utilization and additional morbidity. Penicillin allergy testing of pregnant women with a history of penicillin allergy may help reduce these unwanted outcomes.

Routine coagulation testing in intensive care.

OBJECTIVE: To test a simple clinical guideline to reduce unnecessary routine testing of coagulation status. DESIGN, SETTING AND PARTICIPANTS: A prospective, unblinded, observational study of coagulation testing frequency before and after introduction of a simple clinical guideline. We included 253 patients admitted to a tertiary intensive care unit: 100 patients consecutively enrolled before our intervention (May - July 2015) and 153 patients consecutively enrolled after our intervention (August - September 2015). INTERVENTION: We introduced a clinical guideline and educational program in the ICU from 18 August 2015. MAIN OUTCOME MEASURES: The number of coagulation tests performed per patient bed-day, and the associated pathology costs. RESULTS: Over the 3-month sample period, 999 coagulation profiles were performed for 253 patients: 720 (72%) in 100 patients before, and 279 (28%) in 153 patients after our intervention. The testing frequency fell from 1.12 to 0.41 per patient bed-day (P < 0.001). A total of 463 pre-intervention coagulation profiles (64%) were classified as unnecessary, and the cost of all coagulation tests fell by 60.5% per bedday after the intervention. CONCLUSION: A simple clinical guideline and educational package reduced unnecessary coagulation tests and costs in a tertiary referral ICU.

Fellow Eye Comparisons for 7-Year Outcomes in Ranibizumab-Treated AMD Subjects from ANCHOR, MARINA, and HORIZON (SEVEN-UP Study).

PURPOSE: To compare study and fellow eyes in subjects with age-related macular degeneration (AMD) for 7-year outcomes arising from contrasting treatment histories and disease statuses. DESIGN: Multicenter cohort study, predetermined secondary analysis. PARTICIPANTS: A total of 65 participants from the ranibizumab-treatment arms of the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR), Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA), and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON) trials, recruited for an update evaluation from 14 study sites. METHODS: Seven-year visual outcomes and retinal imaging data were compared with the ANCHOR, MARINA, and HORIZON databases. Under the ANCHOR and MARINA protocols, study eyes had received monthly ranibizumab injections for the initial 2 years, during which fellow eyes were prohibited from anti-vascular endothelial growth factor (VEGF) treatments. MAIN OUTCOME MEASURES: Percentage of subjects with study eye vision better than fellow eye, vision change from baseline to year 7, and mean area of macular atrophy (MA) were predetermined secondary end points. RESULTS: Fellow eyes with exudative AMD had received a mean 7.3 total injections of anti-VEGF agents in the mean 3.4 years off-study. For the 35% of subjects with exudative AMD in both eyes at baseline, within-patient comparisons at year 7 showed better vision in the study eye in 82%, with better mean final vision in study eyes (54.7 vs. 27.3 letters in fellow eyes, P < 0.001). Also in this subgroup, study eyes, which had received 2 years of high-frequency ranibizumab, had less severe MA than the respective fellow eye at year 7 in 88% of patients (mean area ± standard deviation 2.8±2.2 mm(2) vs. 5.8±2.5 mm(2) in the fellow eyes, P = 0.0013). Final fellow eye vision outcome was significantly correlated with MA severity (coefficient -6.95, P < 0.001), and patients' inter-eye vision difference corresponded to the degree of MA asymmetry. CONCLUSIONS: Exudative fellow eyes remained at risk for further vision decline in later years under management with low-frequency anti-VEGF therapy. In patients with bilateral exudative AMD at baseline, final vision at year 7 was significantly better in study eyes than in fellow eyes, and MA was less severe. Macular atrophy area correlated with final visual outcomes, determined inter-eye vision differences, and was not attributable to high-frequency ranibizumab therapy.

Vertical diplopia and ptosis from removal of the orbital roof in pterional craniotomy.

PURPOSE: To describe a newly recognized clinical syndrome consisting of ptosis, diplopia, vertical gaze limitation, and abduction weakness that can occur after orbital roof removal during orbito-zygomatic-pterional craniotomy. DESIGN: Case series. PARTICIPANTS: Eight study patients (7 women), 44 to 80 years of age, with neuro-ophthalmic symptoms after pterional craniotomy. METHODS: Case description of 8 study patients. MAIN OUTCOME MEASURES: Presence of ptosis, diplopia, and gaze limitation. RESULTS: Eight patients had neuro-ophthalmic findings after pterional craniotomy for meningioma removal or aneurysm clipping. The cardinal features were ptosis, limited elevation, and hypotropia. Three patients also had limitation of downgaze and 2 patients had limitation of abduction. Imaging showed loss of the fat layers that normally envelop the superior rectus and levator palpebrae superioris. The muscles appeared attached to the defect in the orbital roof. Ptosis and diplopia developed in 2 patients despite Medpor titanium mesh implants. Deficits in all patients showed spontaneous improvement. In 2 patients, a levator advancement was required to repair ptosis. In 3 patients, an inferior rectus recession using an adjustable suture was performed to treat vertical diplopia. Follow-up a mean of 6.5 years later revealed that all patients had a slight residual upgaze deficit, but alignment was orthotropic in primary gaze. CONCLUSIONS: After pterional craniotomy, ptosis, diplopia, and vertical gaze limitation can result from tethering of the superior rectus-levator palpebrae superioris complex to the surgical defect in the orbital roof. Lateral rectus function sometimes is compromised by muscle attachment to the lateral orbital osteotomy. This syndrome occurs in approximately 1% of patients after removal of the orbital roof and can be treated, if necessary, by prism glasses or surgery.

Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

CONTEXT: Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. OBJECTIVE: To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). METHODS: Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. RESULTS AND DISCUSSION: The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. CONCLUSION: Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

Syphilitic posterior placoid chorioretinitis.

We present a case of syphilitic posterior placoid chorioretinitis, an uncommon but distinct ocular manifestation of syphilis. Because of the ocular findings, a lumbar puncture was performed to evaluate for neurosyphilis, which was positive. The ocular symptoms resolved with intravenous penicillin.

Value of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a safe and accurate technique for diagnosing pancreatic cancer. The value of repeat EUS-FNA in patients with high clinical suspicion for pancreatic cancer after an inconclusive index study is unknown. Our aims were to determine the yield and success of repeat EUS-FNA and the reasons for failure of initial EUS-FNA. METHODS: This was a retrospective analysis of prospectively collected data in a tertiary University based referral center for pancreatico-biliary disorders. All patients who underwent more then one EUS-FNA for evaluation of suspected pancreatic cancer over a five and a half year period were included in this analysis. RESULTS: Of the 547 procedures performed on 517 patients, 24 (4.6%) patients underwent 51 repeat EUS-FNA procedures. Initial EUS-FNA was atypical/suspicious in 10 (41.6%), benign in 10 (41.6%), malignant in two (8.3%), and failed/indeterminate in two (8.3%) patients. Eight of 10 (80%) patients with atypical/suspicious findings at initial EUS-FNA were diagnosed with malignancy on repeat EUS-FNA. Of the 10 patients with benign findings at initial EUS-FNA, repeat study diagnosed two (20%) with malignancy and the rest were confirmed benign on long-term follow up (average 530 days, SD 369 days). Of the two patients with indeterminate findings at initial EUS-FNA, repeat study diagnosed one patient with malignant disease and the other with benign disease that was confirmed by long-term follow up. Of the two patients diagnosed with neoplastic disease at initial EUS-FNA, repeat EUS-FNA with immunostains downgraded both to chronic pancreatitis. Repeat EUS-FNA facilitated determination of the true status of disease in 20 of 24 patients (accuracy 84%). Suspected reasons for failed initial EUS-FNA were: coexisting pancreatitis (n = 10; 42%), technical difficulty due to scope positioning in uncinate lesion/sedation failure (n = 4; 16.7%), difficult cytology (partly cystic, extensive necrosis, well-differentiated adenocarcinoma) (n = 4; 16.7%), presence of ascites or collaterals (n = 3; 12.5%), pathologist's interobserver variation (n = 2; 8.33%), and unknown reason in one patient. CONCLUSION: Repeat EUS-FNA is warranted in patients with high clinical suspicion for pancreatic cancer despite indeterminate or negative findings at initial EUS-FNA.