Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)µg/L(range: 1.4 to 13.4 µg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft.

PURPOSE: The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD). METHODS: We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups. RESULTS: In total, 27 eyes of 22 patients (median age 42 years, range 20-79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) ( P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group ( P = 0.96). The median improvement in BCVA was logMAR -0.975 and logMAR -0.45 for the oral and topical group, respectively ( P = 0.50). CONCLUSIONS: With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.

[Distal pancreatectomy with celiac axis resection for pancreatic body cancer: a single center review of 89 consecutive cases].

Objective: To investigate the clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR). Methods: A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age(M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed,χ2 or Fisher's test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results: Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95%CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95%CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95%CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95%CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion: DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

Synthesis of 6ß-hydroxy androgens from a 3,5-diene steroid precursor to test for cytochrome P450 3A4-catalyzed hydroxylation of androstenedione.

6ß-Hydroxytestosterone is a biomarker for the activity of human cytochrome P450 3A4 (P450 3A4), the major drug metabolizing cytochrome P450 enzyme. Despite its significance, efficient routes for the chemical synthesis of 6ß-hydroxytestosterone are rare. In this study, 6ß-hydroxytestosterone was synthesized through the oxidation of a 3,5-diene precursor under the Uemura-Doyle reaction conditions using a dirhodium catalyst in the presence of tert-butylhydroperoxide. Mechanistic studies showed that some oxygen is incorporated from molecular oxygen and CH abstraction is partially rate-limiting. This reaction was used to synthesize 6ß-hydroxyandrostenedione, which was used as a standard to test the hypothesis of whether P450 3A4 catalyzes the hydroxylation of androstenedione. Upon incubation of P450 3A4 with androstenedione, a hydroxylated product was formed, which matched the retention time of synthetic 6ß-hydroxyandrostenedione. This reaction can be exploited to study other biochemical processes involving compounds with a 6 ß -hydroxy-3-keto-Δ4 steroid backbone.

Synthesis of hyocholic acid and its derivatization with sodium periodate to distinguish it from cholic acid by mass spectrometry.

Low concentrations of hyocholic acid in human serum has been linked to diabetes. Due to its important role in human health, we were interested in synthesizing hyocholic acid to explore potential biochemical properties of this bile acid. Here, a synthesis of hyocholic acid is reported from chenodeoxycholic acid. The key step was a Rubottom oxidation of a silyl enol ether intermediate to directly incorporate the oxygen at C6. Furthermore, the synthesized hyocholic acid product was treated with NaIO4 to cleave the C6-C7 bond to yield a hemiacetal at C6. This CC bond cleavage reaction using NaIO4 was used to develop an ultra-performance liquid chromatography mass spectrometry method to distinguish between a 1 to 1 mixture of hyocholic acid and cholic acid (a 12α-hydroxylated bile acid), two bile acid regioisomers with identical masses. Upon treatment of the mixture with NaIO4, hyocholic acid was selectively cleaved in the B ring (C6-C7 bond) to yield the hemiacetal that formed between the C3-hydroxy and the C6-aldehyde moiety with an m/z 405 while cholic acid remained intact with an m/z 407 in the negative electrospray ionization mode. Subsequently, a commercially available ox bile extract was treated with NaIO4 to detect bile acid derivatives by mass spectrometry. Two possible hyocholic acid derivatives conjugated to serine and gamma-glutamic semialdehyde were detected in electrospray ionization positive mode, which oxidatively cleaved with NaIO4 (m/z 496 and 522 to m/z 494 and 520, respectively).

Clinical applications of bioengineered tissue-cellular products for management of corneal diseases.

PURPOSE OF REVIEW: To discuss bioengineered tissue-cellular products for treatment of corneal diseases that are currently in clinical use. These include tissue-cellular products that have received regulatory approval, are being used off-label in clinical practice, or are in active use in clinical trials. RECENT FINDINGS: Due to the global shortage of donor corneal tissue, significant efforts have been made to develop bioengineering tissue-cellular products that can replace or augment the use of cadaveric tissue for corneal transplantation. The development of carrier substrates to support transplantation of cultivated limbal epithelial transplantation (CLET) has been a growing area of research. CLET offers a promising therapeutic alternative to conventional simple limbal epithelial transplantation and keratolimbal allografts for treatment of limbal stem cell deficiency. Engineered tissue matrices and porcine-derived corneas are potential alternatives to human donor tissue in anterior lamellar keratoplasty for corneal ulcers and scars, as well as intrastromal transplants for advanced keratoconus. For endothelial disease, substrate supported cultured endothelial cell grafts, and synthetic barrier devices are promising alternative to traditional endothelial keratoplasties. SUMMARY: There has been increasing interest in cellular and acellular bioengineered tissue-cellular and synthetic products for treatment of corneal diseases, and many of these products have already seen clinical use. Industry and academia have important roles in advancing these products to later phase clinical trials and comparing them to conventional allograft approaches. Future development of full thickness donor corneas with cultivated epithelium, endothelium, and stromal keratocytes in a biosynthetic matrix will likely be an important next step in tissue alternatives. Continued progress in this field will be critical for addressing the global disease burden from corneal blindness.

Update on Femtosecond Laser-Enabled Keratoplasty.

ABSTRACT: The application of femtosecond lasers to corneal transplantation is an intriguing proposition with many potential benefits to patients with various corneal diseases. The customized trephination pattern for donor and host matching offers many advantages regarding wound integrity and high precision of donor and recipient match at the interface, which should lead to faster healing and visual rehabilitation. Femtosecond laser-enabled keratoplasty (FLEK) is an advancement of conventional trephination penetrating keratoplasty, and in large clinical cohorts to date, there are meaningful improvements in visual outcomes and a lower risk of graft rejection. Femtosecond laser-enabled deep anterior lamellar keratoplasty (Femto-DALK) combines the advantage of a customized trephination pattern with the deep anterior lamellar keratoplasty procedure, which eliminates the risk of endothelial rejection. Furthermore, the precision of the femtosecond laser may offer additional novel approaches to lamellar keratoplasties. In time, advancements in femtosecond laser platforms will help cornea surgeons realize the added benefits and better optimize outcomes for patients, such that the cost-benefit calculus shifts toward wider accessibility for patients. Prospective randomized-controlled trials are needed to definitively determine the impact of femtosecond laser-enabled keratoplasties on long-term outcomes.

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial.

PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM. DESIGN: Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial. PARTICIPANTS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS: Patients received uniocular subfoveal injections of low-dose (up to 5 × 1010 vector genome [vg] per eye, n = 5) or high-dose (up to 1 × 1011 vg per eye, n = 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing. MAIN OUTCOME MEASURES: Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (< 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.

[Comparative clinical efficacy analysis of pancreatoduodenectomy for distal bile duct and pancreatic head cancer: a report of 1 005 cases].

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ2 test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.

Downbeat nystagmus: a clinical review of diagnosis and management.

PURPOSE OF REVIEW: This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). RECENT FINDINGS: Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. SUMMARY: DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

Access route selection for percutaneous coronary intervention among Vietnamese patients: Implications for in-hospital costs and outcomes.

BACKGROUND: Little is known about rates of access site (transradial (TRI) or transfemoral (TFI)) preference for percutaneous coronary intervention (PCI) and in-hospital costs of patients undergoing these procedures in lower-and middle-countries. Here, we report on access site use, in-hospital costs and outcomes of patients undergoing PCI in Vietnam. METHODS: Information from 868 patients were included in the cohort of 1022 patients recruited into the first PCI registry in Vietnam. The total hospital costs and in-hospital outcomes of patients undergoing TRI and TFI were compared. Hospital costs were obtained from the hospital admission system, and major adverse cardiac events, major bleeding events and length of stay were identified through review of medical records. FINDINGS: TRI was the dominant access site for interventionists (694/868 patients). The TFI group reported more lesions of the left main artery, more previous coronary artery bypass grafts and previous PCI in comparison with the TRI group (all p < 0.05). The TRI group was associated with a lower overall cost of admission (the adjusted difference was -1526.3 USD, 95% confident interval CI (-1996.2; -1056.3), shorter length of hospital stay (-2 days, CI (-2.8; -1.2)) and lower rates of major bleeding post-procedure. Procedural factors such as radial access site, left main disease, PCI ≥2 stents, and PCI ≥ 2 lesions having the most impact on the in-hospital cost of patients undergoing PCI. INTERPRETATIONS: Among patients undergoing PCI, TRI was associated with lower costs and favourable clinical outcomes relative to TFI. FUNDING: This research received partial financial support from Curtin University, Australia.

Outcomes following the percutaneous coronary intervention in contemporary Vietnamese practice: Insight from a single centre prospective cohort.

BACKGROUND: Evidence regarding the outcomes of percutaneous coronary intervention (PCI) in low-and-middle incomes countries remains limited. OBJECTIVES: To report the outcomes post PCI at discharge, 30 days and 12 months in Vietnam and identify the key factors associated with adverse outcomes at 12 months. METHODS: We used data from a single centre prospective cohort in Vietnam. Data regarding demographics, clinical presentation, procedural information, and outcomes of patients were collected and analysed. Primary outcomes were mortality and major adverse cardiac and cerebrovascular events. RESULTS: In total, 926 patients were included. Poor outcomes were relatively low in those undergoing PCI. Predictors of mortality and major adverse cardiac and cerebrovascular events at 12 months post-PCI included being older than 75, being male, having acute myocardial infarction, left ventricular ejection fraction ≤ 40%, prior cerebral vascular disease and having an unsuccessful PCI. CONCLUSIONS: Adverse outcomes of patients undergoing PCI in Vietnam are relatively low in comparison with those reported in other countries across the Asia Pacific region. Identification of factors associated with poor outcomes is beneficial for improving the quality of cardiac care and developing the prediction model of outcomes post-PCI in Vietnam.

Teaching Smartphone Funduscopy with 20 Diopter Lens in Undergraduate Medical Education.

PURPOSE: To assess attitudes of pre-clinical undergraduate medical students toward learning smartphone funduscopy (SF) and its appropriateness as a teaching tool. PATIENTS AND METHODS: Second year medical students received instruction on direct ophthalmoscopy (DO) and SF; they were then paired with a peer and randomly assigned to perform DO or SF first. The SF technique involved freehand alignment of the axes of the smartphone camera with a condenser lens. Both techniques were done through a maximally dilated pupil. A questionnaire was completed to acquire data on baseline experience, performance of both examination techniques, attitudes, and appropriateness. Statistical significance testing and Bland-Altman analysis were used to determine differences between DO and SF, and a multivariable mixed regression model was fitted to identify any predictors for positive attitudes toward DO or SF. RESULTS: One hundred thirty-seven (137) individuals completed the study. A similar proportion of students could identify the optic nerve, macula, and vessels using DO and SF. However, self-reported quality scores were higher for DO for the optic nerve (p = 0.006) and macula (p = 0.08). The mean (standard deviation) attempts to identify these major structures were 2.7 (SD 2.3) for DO and 4.5 (SD 2.9) for SF (p < 0.001). Attitudes of students were consistently more positive toward DO across the five questions assessed. A small subset of students had equally positive attitudes toward DO and SF. Improved quality scores were predictive of positive attitudes for both DO and SF. Ultimately, 24% of students preferred SF over DO. CONCLUSION: Among inexperienced examiners of the fundus through a dilated pupil, SF is a non-inferior technique to DO in identifying structures. Despite overall favorable attitudes towards the more familiar DO, those students who quickly learned the SF technique had similar satisfaction scores. Teaching SF should be considered in undergraduate medical education.

Cancer-Associated Retinopathy due to Clear Cell Renal Carcinoma.

An 84-year-old female presented with bilateral scotomas and progressive nyctalopia over 1 year. Best-corrected visual acuity was 20/50 in both eyes with reduced color vision. Goldmann visual field showed bilateral cecocentral scotomas and generalized constriction of the visual fields. This led to an electroretinogram showing an electronegative pattern consistent with autoimmune retinopathies. Infectious workup was negative. Anti-retinal antibodies were positive, leading to a presumed diagnosis of cancer-associated retinopathy (CAR). Imaging showed a previously unknown left renal lower pole mass, and she underwent a radical nephrectomy. Biopsy showed nuclear grade-3 clear cell renal carcinoma staged T1. The patient was treated with oral prednisone with no ocular improvement. We report on a rare case of clear cell renal carcinoma causing CAR. CAR is an important paraneoplastic syndrome to diagnose since the majority of ocular cases precede other manifestations of malignancy. Therefore, a timely diagnosis of CAR can be lifesaving or at least life-extending.

Smartphone-based Ophthalmic Imaging Compared With Spectral-domain Optical Coherence Tomography Assessment of Vertical Cup-to-disc Ratio Among Adults in Southwestern Uganda.

PRECIS: Using optical coherence tomography (OCT) measurements as a reference standard for vertical cup-to-disc ratio (vCDR), a smartphone-based ophthalmic camera has a sensitivity of 67.7% and specificity of 96.7% to detect a vCDR>0.5. PURPOSE: The purpose of this study was to assess the performance of a smartphone-based ophthalmic camera system using an Apple iPhone 6S and an adapter, Paxos Scope, to obtain adequate dilated fundus photos to measure clinically useful vCDR cutoffs. PATIENTS AND METHODS: Adult patients from a government tertiary level eye hospital in Southwestern Uganda were prospectively recruited from January to April 2019. All patients experienced a comprehensive eye examination, dilated posterior segment indirect ophthalmoscope imaging with the Paxos Scope, and spectral-domain OCT imaging with a Cirrus HD-OCT to measure vCDR. Patients' eyes excluded had media opacities or existing disease precluding a view of the fundus. Fundus images underwent a single masked review to assign vCDR at increments of 0.1. Descriptive statistics, parametric and χ2 tests for significance, repeated measures correlation, κ, receiver operating characteristics curve, and Bland-Altman were used to assess the data. RESULTS: Among 467 (consecutive) individuals, fundus photographs acquired with the Paxos Scope demonstrated a 67.7% [95% confidence interval (CI), 63.0-72.0] sensitivity and 96.7% (95% CI, 94.2-98.3) specificity to detect a vCDR>0.5, using OCT as the reference standard. A total of 138 eyes were excluded due to poor imaging acquisition, such as dense cataract, rendering 796 eyes for analysis. The vCDR from graded Paxos Scope images and OCT correlated well with repeated measures correlation of 0.82 (95% CI, 0.77-0.86, P<0.001) and agreement, dichotomized as >0.5 or ≤0.5, was 80.9% (κ=0.63±0.034, P<0.001). Among glaucoma and glaucoma suspects (85 eyes), the sensitivity and specificity dichotomized using vCDR>0.5 were 97.5% (95% CI, 91.3-99.7) and 80.0% (95% CI, 28.4-99.5), respectively. The area under the receiver operating characteristics curve was 0.92 (95% CI, 0.89-0.94) for all eyes and 0.98 (95% CI, 0.78-1.0) for glaucoma and glaucoma suspects. CONCLUSIONS: The Paxos Scope produced images that can be reliably used to estimate vCDR, which is closely aligned with the automated algorithm from the OCT optic disc cube scan. The low-cost, ready-to-integrate adapter, and minimal training requirements make it a viable option for population-based screening in low-resource settings.

Age Estimation in Han Adults by Thin-Layer CT Scan of Cranial Sutures.

ABSTRACT: Objective To explore the value of degree of cranial suture closure in forensic adult age estimation by thin-layer CT scan and establish an adult age estimation model of the Han nationality. Methods Thin-layer CT scan samples of the heads of 220 healthy Sichuan Han adults （110 males, 110 females） aged 20 to 70 were collected, of which 20 samples （10 males, 10 females） were randomly selected as test samples. The sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） were respectively and equally divided into 2 segments, and every segment was equally divided into 10 layers and the corresponding multiplanar reformation （MPR） images were selected. The closure of cranial sutures on MPR images was classified into the grades 1-7. The correlations between cranial sutures and age were analyzed to build regression equation for age estimation. Results The degree of closure of sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） was positively correlated with age. The coefficient of determination （R2） of regression equation was 0.419 in males, 0.589 in females, and 0.522 in all samples. The results of the verification test showed that the mean absolute error （MAE） was 6.39 years in males, 6.16 years in females, and 6.29 years in all samples. Conclusion There was a higher accuracy in adult age estimation by thin-layer CT scan of cranial sutures. The age of Han nationality adults can be estimated by the degree of cranial sutures closure.

Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.

Purpose: To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD). Methods: The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis. Results: Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001). Conclusions: In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.

Resonant Inelastic X-Ray Scattering Reveals Hidden Local Transitions of the Aqueous OH Radical.

Resonant inelastic x-ray scattering (RIXS) provides remarkable opportunities to interrogate ultrafast dynamics in liquids. Here we use RIXS to study the fundamentally and practically important hydroxyl radical in liquid water, OH(aq). Impulsive ionization of pure liquid water produced a short-lived population of OH(aq), which was probed using femtosecond x-rays from an x-ray free-electron laser. We find that RIXS reveals localized electronic transitions that are masked in the ultraviolet absorption spectrum by strong charge-transfer transitions-thus providing a means to investigate the evolving electronic structure and reactivity of the hydroxyl radical in aqueous and heterogeneous environments. First-principles calculations provide interpretation of the main spectral features.