bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy Complicated With a Giant Pancreatic Tumor and Decompensation of Liver Cirrhosis: A Case Report and Literature Review
Authors: Yu Yi , Teng Lirong , Liu Juntao , Liu Xinyan , Peng Ping , Zhou Qian , Liu Congcong
Published: February 2023

Pregnancy with solid pseudopapillary tumor of the pancreas (SPTP) is rare. Because pregnancy hormones may cause tumor progression, the management and treatment of SPTP need to balance the safety of pregnant women and fetuses with surgical treatment. We reported a case of a giant pancreatic tumor diagnosed during pregnancy that was considered to be SPTP. Examinations also showed hepatitis B virus infection and severe decompensation of liver cirrhosis. Medical termination of pregnancy was performed. The patient has lived with the tumor until now without surgery. We retrieved the published case reports, summarized the clinical characteristics of pregnancy with SPTP, and explored its management during the perinatal period. Most patients with SPTP have a good prognosis with good maternal and fetal outcomes, and it is important to choose an appropriate treatment method and timing. However, pregnancy combined with decompensated liver cirrhosis needs to be terminated in a timely manner because of its high-risk status.
Urban-rural differences in epidemiology and risk factors of menopause syndrome in middle-aged Chinese women
Authors: An Junxia , Li Lifei
Published: February 2023

Objective

To compare the prevalence and severity of menopausal symptoms and investigate their associated factors among rural and urban middle-aged Chinese women.

Methods

A descriptive, cross-sectional study of 4,580 urban and 2,729 rural randomly sampled participants aged 40 to 55 years in Gansu Province, China, was conducted. Questionnaires assessing the sociodemographic information and menstrual and reproductive histories of the participants were administered. The modified Kupperman scale was used to assess the presence and severity of menopausal symptoms. Binary and ordinal logistic regression analyses were performed to identify factors associated with the occurrence and severity of menopausal syndrome, respectively, according to the modified Kupperman Menopausal Index score rank.

Results

The natural menopausal age of the rural women was significantly lower than that of the urban women (rural: 47.22, urban: 47.98; P < 0.05). Furthermore, rural women had a higher prevalence (rural: 56.35%, urban: 43.47%) and severity (rural: 11.40%, urban: 6.61%) of menopausal syndrome than the urban women (P < 0.05). For both the urban and rural women, the prevalence and severity of most menopausal symptoms increased as menopause progressed. The three most prevalent symptoms in both the urban and rural women were fatigue (rural: 70.43%, urban: 68.19%), muscle/joint pain (rural: 62.84%, urban: 59.32%), and vertigo (rural: 57.42%, urban: 47.44%). Positive associations between menopausal symptoms and age, residence, body mass index, level of education, time of pregnancy, menstrual cycle, and presence of chronic diseases were observed.

Conclusions

Rural women experience more frequent and severe menopausal syndrome than do urban women.
Effectiveness of vaginal estriol with lactobacilli on urinary symptoms in postmenopausal women: a randomized-controlled trial
Authors: Jongjakapun Apiwat , Somboonporn Woraluk , Temtanakitpaisan Teerayut
Published: February 2023

Objective

The aim of this study was to compare the effects of a vaginal tablet containing estriol (0.03 mg) plus lactobacilli (E3/L) with placebo on lower urinary tract symptoms (LUTS) in postmenopausal women (PMW).

Methods

This randomized, double-blinded, placebo-controlled trial was conducted at Srinagarind Hospital in Khon Kaen, Thailand. PMW with at least one LUTS, such as frequency, nocturia, dysuria, urgency, or stress or urgency urinary incontinence, were recruited. Participants were randomly assigned to receive either an E3/L tablet or placebo, administered vaginally daily at bedtime for 2 weeks, then twice a week for another 2 weeks. Symptom severity score was assessed using a visual analog scale (VAS), and quality of life (QOL) was measured using the validated Thai version of the Incontinence Impact Questionnaire-Short Form. The primary outcome was proportion of the PMW with LUTS improvement. Secondary outcomes were symptom severity score, participant satisfaction, QOL, and adverse events. Relative risk and 95% confidence intervals (CIs) were calculated using the chi-square or Fisher's exact test. An independent-sample and paired t test were used to compare means.

Results

Thirty-eight participants in each group completed the study. The proportion of PMW whose symptoms improved (both in terms of most bothersome symptom and overall) did not differ significantly between the two groups. Relative risk was 1.00 (95% CI, 0.74-1.36) and 0.90 (95% CI, 0.71-1.15), respectively. There were no differences in symptom severity score, participant satisfaction, or QOL.

Conclusions

A 1-month course of vaginal E3/L does not appear to improve LUTS in PMW.
Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study
Authors: Hull Louise , Stuckey Bronwyn G. A. , Hartman Kimberly , Zack Nadene , Friend David R.
Published: February 2023

Objective

The aim of this work is to develop a combination of 17β-estradiol (E2) and progesterone (P4) in a single-dose intravaginal ring (IVR) for the treatment of vasomotor symptoms (VMS) and genitourinary syndrome of menopause while providing endometrial protection. The objective of this study was to evaluate DARE-HRT1, a 28-day IVR that continuously delivers E2 and P4, in a phase 1 clinical trial to assess its pharmacokinetics.

Methods

This was an open-label, three-arm (group) study. Thirty-two (32) healthy postmenopausal women were recruited at two Australian sites. The average age was 57.2 years (47-69 y). The first arm received one ring for 28 days designed to release E2 at a rate of 80 μg/d and P4 at 4 mg/d (80/4 IVR); the second arm received a ring releasing E2 at 160 μg/d and P4 at 8 mg/d (160/8 IVR). The third arm received oral Estrofem (1 mg E2) and Prometrium (100 mg P4) both daily for 29 days. Blood samples were taken predose then intensively over the first day (day 1) and periodically thereafter over the remaining 27 days. After removal of the rings on the morning of day 29, intensive samples were collected. Similar procedures were conducted with women enrolled in the oral group. The plasma samples were analyzed for E2, estrone (E1), and P4 using validated bioanalytical methods.

Results

The baseline-adjusted steady-state plasma levels of E2 and P4 from 80/4 IVR were 20.4 ± 17.1 pg/mL and 1.32 ± 0.19 ng/mL (n = 10), respectively. The baseline-adjusted steady-state plasma levels of E2 and P4 from 160/8 IVR were 30.9 ± 8.7 pg/mL and 2.08 ± 0.50 ng/mL (n = 10), respectively. The baseline-adjusted average plasma concentrations of E2 and P4 at day 29 of the oral group were 35.4 ± 11.2 pg/mL and 0.79 ± 0.72 ng/mL (n = 11), respectively. The baseline-adjusted steady state of E1 from the 80/4 IVR and the 160/8 IVR were 22.1 ± 16.6 pg/mL (n = 10) and 25.2 ± 12.3 pg/mL (n = 10), respectively. The baseline-adjusted concentration of E1 in the oral arm was 209 ± 67.7 ng/mL (n = 11). The IVR were well tolerated, and no serious adverse events were reported.

Conclusions

The 80/4 IVR and 160/8 IVR gave similar steady-state concentrations of E2 as seen with drug products approved by the US Food and Drug Administration for treatment of VMS and genitourinary symptoms of menopause. The E2 concentrations of this study support the potential of DARE-HRT1, a promising new option for hormone therapy for treatment of VMS and vaginal symptoms associated with menopause.
Effect of ospemifene on vaginal microbiome in postmenopausal women with vulvovaginal atrophy
Authors: Alvisi Stefania , Ceccarani Camilla , Foschi Claudio , Baldassarre Maurizio , Lami Alessandra , Severgnini Marco , Camboni Tania , Consolandi Clarissa , Seracchioli Renato , Meriggiola Maria Cristina
Published: February 2023

Objectives

This study aimed (i) to compare the vaginal microbiome profiles of women suffering from vulvovaginal atrophy with that of healthy postmenopausal women and to (ii) assess the effect of ospemifene and systemic hormone treatment on the composition of the vaginal microbiome.

Methods

Sixty-seven postmenopausal women attending the Gynecology Clinic of Azienda Ospedaliero-Universitaria of Bologna (Italy) were enrolled. Of them, 39 received a diagnosis of atrophy and 28 were considered healthy controls. In the group of atrophic women, 20 were prescribed ospemifene and 19 received hormone treatment. The vaginal health index was calculated, and a vaginal swab was collected for the assessment of vaginal maturation index and the analysis of vaginal microbiome through 16S rRNA gene sequencing. Clinical/microbiological analyses were repeated after 3 months of treatment.

Results

The vaginal microbiome of atrophic women was characterized by a significant reduction of Lactobacillus (P = 0.002) and an increase of Streptococcus (P = 0.008) and Sneathia (P = 0.02). A positive correlation between vaginal health index/vaginal maturation index and Lactobacillus abundance was found (P = 0.002 and P = 0.035, respectively). Both therapeutic approaches effectively improved vaginal indices. Systemic hormone treatment induced changes in minority bacterial groups of the vaginal microbiome, whereas ospemifene was able to eliminate specific bacterial taxa, such as Staphylococcus (P = 0.04) and Clostridium (P = 0.01). Both treatments induced a trend in the increase of bifidobacteria.

Conclusions

The vaginal microbiome of atrophic women differs significantly from that of healthy postmenopausal women. Ospemifene may lead to a condition of vaginal health, likely characterized by the reduction of “potentially harmful” bacteria.
The Impact of Travel Distance and Income on Breast Reconstruction after Mastectomy in a Rural Population
Authors: Clegg Devin J. , Salomon Brett J. , Porter Christopher G. , Mazonas Thomas W. , Heidel Robert E. , Chun Joseph T. , Herbig Kathleen S. , Stephenson Stacy M. , Lloyd Jillian M. , Boukovalas Stefanos
Published: February 2023

Background:

Factors that influence breast reconstruction after mastectomy have been previously examined in national databases. The purpose of this study was to determine the impact of patient travel distance and income on breast reconstruction after mastectomy in a rural population.

Methods:

Retrospective review of mastectomy patients from 2017 to 2021 was performed from our prospectively enrolled tumor registry. Analysis included frequencies and percentages, descriptive statistics, χ
2 analysis, independent sample t tests, and multivariable analysis.

Results:

In total, 462 patients were included. Median BMI was 27.6 kg/m2, 96.1% of patients were White, and median age at diagnosis was 60.0 years. Reconstruction rate was 52.6%, and median length of follow-up was 24.6 months. No significant difference was found in the distance traveled by patients who underwent reconstruction (16.6 versus 16.7 miles; P = 0.94). Rates of reconstruction in patients who traveled 0–10 miles, 11–30 miles, and over 30 miles did not differ significantly (P = 0.16). Median household income was significantly different in reconstructed and nonreconstructed patients ($55,316.00 versus $51,629.00; P = 0.047). Rates of reconstruction were significantly higher in patients with median household income greater than $65,000 (P = 0.024). This difference was not significant on multivariable analysis.

Conclusions:

Travel distance did not significantly impact reconstruction rates after mastectomy, while household income did on univariable analysis. Studies at an institutional or regional level remain valuable, especially in populations that may not be accurately represented in larger database studies. Our findings highlight the importance of patient education, resource allocation, and multidisciplinary approach to breast cancer care, especially in the rural setting.
Methods to Account for CAP-88 PC-Omitted Nuclides in Radioactive Air Emissions From DOE Facilities
Authors: Harshman Amber , Scofield Patricia
Published: February 2023

Routine research and development activities at US Department of Energy facilities can result in the release of radioactive emissions, potentially exposing the public and the environment. Such emissions are subject to certain Clean Air Act regulations, specifically those outlined in 40 CFR Part 61, Subpart H, which are enforced by the US Environmental Protection Agency. Compliance is determined in part with a dose standard. Doses to members of the public from most US Department of Energy facility airborne emissions are modeled using CAP-88 PC software, the latest version of which contains more than 1,200 radionuclides. Radioactive effluents from US Department of Energy facilities may contain radioisotopes that are not available in CAP-88 PC, and those radioisotopes must still be evaluated to determine whether doses to members of the public are below established limits. CAP-88 PC-omitted radionuclides can be accounted for using alternate methods, including the use of surrogate radionuclides. This paper elucidates the process of accounting for CAP-88 PC-omitted radionuclides by providing criteria and rationale for surrogate selection, a compilation of surrogate radionuclides used in the past by US Department of Energy facilities, a discussion of alternate methods used to account for CAP-88 PC-omitted radionuclides and a comparison of methods and impacts on receptor doses. Ultimately, this paper aims to aid in the process of surrogate selection and consequently to simplify and expedite compliance with Clean Air Act regulations.
Particle Size Dependent Dissolution of Uranium Aerosols in Simulated Gastrointestinal Fluids
Authors: Yusuf Ibtisam , Hansson Edvin , Eriksson Mats , Roos Per , Lindahl Patric , Pettersson Håkan B. L.
Published: February 2023

Uranium aerosol exposure can be a health risk factor for workers in the nuclear fuel industry. Good knowledge about aerosol dissolution and absorption characteristics in the gastrointestinal tract is imperative for solid dose assessments and risk management. In this study, an in vitro dissolution model of the GI tract was used to experimentally study solubility of size-fractionated aerosols. The aerosols were collected from four major workshops in a nuclear fuel fabrication plant where uranium compounds such as uranium hexafluoride (UF6), uranium dioxide (UO2), ammonium uranyl carbonate, AUC [UO2CO3·2(NH4)2CO3] and triuranium octoxide (U3O8) are present. The alimentary tract transfer factor, fA, was estimated for the aerosols sampled in the study. The transfer factor was derived from the dissolution in the small intestine in combination with data on absorption of soluble uranium. Results from the conversion workshop indicated a fA in line with what is recommended (0.004) by the ICRP for inhalation exposure to Type M materials. Obtained transfer factors, fA, for the powder preparation and pelletizing workshops where UO2 and U3O8 are handled are lower for inhalation and much lower for ingestion than those recommended by the ICRP for Type M/S materials fA = 0.00029 and 0.00016 vs. 0.0006 and 0.002, respectively. The results for ingestion and inhalation fA indicate that ICRP’s conservative recommendation of fA for inhalation exposure is applicable to both ingestion and inhalation of insoluble material in this study. The dissolution- and subsequent absorption-dependence on particle size showed correlation only for one of the workshops (pelletizing). The absence of correlation at the other workshops may be an effect of multiple chemical compounds with different size distribution and/or the reported presence of agglomerated particles at higher cut points having more impact on the dissolution than particle size. The impact on dose coefficients [committed effective dose (CED) per Bq] of using experimental fA vs. using default fA recommended by the ICRP for the uranium compounds of interest for inhalation exposure was not significant for any of the workshops. However, a significant impact on CED for ingestion exposure was observed for all workshops when comparing with CED estimated for insoluble material using ICRP default fA. This indicates that the use of experimentally derived site-specific fA can improve dose assessments. It is essential to acquire site-specific estimates of the dissolution and absorption of uranium aerosols as this provides more realistic and accurate dose- and risk-estimates of worker exposure. In this study, the results indicate that ICRP’s recommendations for ingestion of insoluble material might overestimate absorption and that the lower fA found for inhalation could be more realistic for both inhalation and ingestion of insoluble material.
DynamicMC: An Open-source GUI Program Coupled with MCNP for Modeling Relative Dynamic Movement of Radioactive Source and ORNL Phantom in a 3-dimensional Radiation Field
Authors: Yu Kwan Ngok , Watabe Hiroshi , Zivkovic Milena , Krstic Dragana , Nikezic Dragoslav , Kim Kyeong Min , Yamaya Taiga , Kawachi Naoki , Tanaka Hiroki , Haque A.K.F. , Shahmohammadi Beni Mehrdad
Published: February 2023

The present work introduces an open-source graphical user interface (GUI) computer program called DynamicMC. The present program has the ability to generate ORNL phantom input script for the Monte Carlo N-Particle (MCNP) package. The relative dynamic movement of the radiation source with respect to the ORNL phantom can be modeled, which essentially resembles the dynamic movement of source-to-target (i.e., human phantom) distance in a 3-dimensional radiation field. The present program makes the organ-based dosimetry of the human body much easier, as users are not required to write lengthy scripts or deal with any programming that many may find tedious, time consuming, and error prone. In this paper, we have demonstrated that the present program can successfully model simple and complex relative dynamic movements (i.e., those involving rotation of source and human phantom in a 3-dimensional field). The present program would be useful for organ-based dosimetry and could also be used as a tool for teaching nuclear radiation physics and its interaction with the human body.
Interim Positron Emission Tomography During Frontline Chemoimmunotherapy for Follicular Lymphoma
Authors: Merryman Reid W. , Michaud Laure , Redd Robert , Mondello Patrizia , Park Hyesun , Spilberg Gabriela , Robertson Matthew , Taranto Eleanor , Ahmed Gulrayz , Chase Matthew , Jeter Erin , Ahn Inhye E. , Brown Jennifer R. , Crombie Jennifer , Davids Matthew S. , Fisher David C. , Jacobsen Eric , Jacobson Caron A. , Kim Austin I. , LaCasce Ann S. , Ng Samuel Y. , Odejide Oreofe O. , Parry Erin M. , Salles Gilles , Zelenetz Andrew D. , Armand Philippe , Schöder Heiko , Jacene Heather
Published: February 2023

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1–3A FL who had an interim PET after 2–4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS (P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET (P < 0.001) and progression of disease within 24 months (POD24) (P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS (P < 0.001) or ΔSUVmax75% (P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL.
Comparison of Frailty Indices and the Charlson Comorbidity Index in Traumatic Brain Injury
Authors: Maragkos Georgios A. , Matsoukas Stavros , Cho Logan D. , Legome Eric L. , Wedderburn Raymond V. , Margetis Konstantinos
Published: February 2023

Background:

Comorbidity scales for outcome prediction in traumatic brain injury (TBI) include the 5-component modified Frailty Index (mFI-5), the 11-component modified Frailty Index (mFI-11), and the Charlson Comorbidity Index (CCI).

Objective:

To compare the accuracy in predicting clinical outcomes in TBI of mFI-5, mFI-11, and CCI.

Methods:

The National Trauma Data Bank (NTDB) of the American College of Surgeons (ACS) was utilized to study patients with isolated TBI for the years of 2017 and 2018. After controlling for age and injury severity, individual multivariable logistic regressions were conducted with each of the 3 scales (mFI-5, mFI-11, and CCI) against predefined outcomes, including any complication, home discharge, facility discharge, and mortality.

Results:

All 3 scales demonstrated adequate internal consistency throughout their individual components (0.63 for mFI-5, 0.60 for CCI, and 0.56 for mFI-11). Almost all studied complications were significantly more likely in frail patients. mFI-5 and mFI-11 had similar areas under the curve (AUC) for all outcomes, while CCI had lower AUCs (0.62-0.61-0.53 for any complication, 0.72-0.72-0.52 for home discharge, 0.78-0.78-0.53 for facility discharge, and 0.71-0.70-0.52 for mortality, respectively).

Conclusion:

mFI-5 and mFI-11 demonstrated similar accuracy in predicting any complication, home discharge, facility discharge, and mortality in TBI patients across the NTDB. In addition, CCI's performance was poor for the aforementioned metrics. Since mFI-5 is simpler, yet as accurate as the 2 other scales, it may be the most practical both for clinical practice and for future studies with the NTDB.
OUTER RETINAL TUBULATION IN BIETTI CRYSTALLINE DYSTROPHY ASSOCIATED WITH THE RETINAL PIGMENT EPITHELIUM ATROPHY
Authors: Wang Yusong , Chen Jieqiong , Sun Junran , Li Tong , Yu Suqin , Gong Yuanyuan , Yu Yang , Wan Xiaoling , Jia Huixun , Wu Jihong , Yuan Fei , Shen Xi , Wang Zhiliang , Qiao Tong , Wu Qiang , Xu Yu , Wang Zhaoyang , Yang Chenhao , Qu Jifang , Chen Jianjun , Sun Xiaodong ,   Shanghai Inherited Retinal Diseases (SHIRD) Study Group
Published: February 2023

Purpose:

To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD).

Methods:

This retrospective, multicenter cohort study enrolled 42 patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location, and morphologic characteristics were analyzed.

Results:

Forty-two patients with BCD harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, 9 of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in Stage 2 than other stages (P < 0.001). ORT was mainly bilateral and located at the margin of the atrophic area of retinal pigment epithelium (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT (P = 0.017), with significantly longer intact RPE width in Stage 3 (P = 0.024). Eyes with ORT had slower vision loss than eyes without ORT (P = 0.044).

Conclusion:

ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.
PATTERNS OF SUBRETINAL AND/OR INTRARETINAL FLUID RECURRENCE IN PATIENTS WHO RECEIVED AS-NEEDED RANIBIZUMAB THERAPY IN THE HARBOR TRIAL
Authors: Adrean Sean D. , Chaili Siyang , Hill Lauren , Amador-Patarroyo Manuel J.
Published: February 2023

Purpose:

To evaluate subretinal fluid (SRF) and/or intraretinal fluid recurrence in patients with neovascular age-related macular degeneration who received as-needed (PRN) ranibizumab in a HARBOR (NCT00891735) post hoc analysis.

Methods:

Analyses included patients with SRF and/or intraretinal fluid at baseline and fluid recurrence after a ≥3-month absence (N = 222). Baseline fluid location(s) were compared with location of recurrence after a ≥3-month absence.

Results:

At baseline, fluid was equally distributed across all locations. On recurrence, the location was most frequently central (69%). Eyes with central fluid at baseline typically had recurrence in the same location (72% vs. 47%–53% with fluid in other locations). The type of recurrent fluid was typically the same as at baseline (SRF, 64%; intraretinal fluid, 75%). Overall, 37% (39/105) of eyes exhibited fluid recurrence in a new location, most frequently central (53%). There was a significant gain in best-corrected visual acuity (mean [95% confidence interval], +2.2 [0.4–4.0] letters) between the months of SRF resolution and recurrence.

Conclusion:

Although the location of SRF and/or intraretinal fluid was equally distributed at baseline, recurrent fluid was typically centrally located. The authors identified a subgroup of eyes exhibiting fluid recurrence in a different location than at baseline, potentially indicating new choroidal neovascularization.
DEFINING “STRONG” VERSUS “WEAK” RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA
Authors: Sun Jennifer K. , Beaulieu Wesley T. , Melia Michele , Ferris Frederick L. , Maturi Raj K. , Nielsen Jared S. , Solomon Sharon D. , Jampol Lee M. ,   for the DRCR Retina Network
Published: February 2023

Background/Purpose:

To define “strong” versus “weak” antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME).

Methods:

Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25–20/32, 20/40–20/63, or 20/80–20/320, respectively. Thresholds of 50, 100, or 200-µm reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175-µm above standard thresholds. Additional thresholds from regression equations were calculated.

Results:

At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations.

Conclusion:

These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.
LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS
Authors: Rohart Charlotte , Le Hoang-Mai , Estrada-Walker Juliana , Giocanti-Auregan Audrey , Cohen Salomon Y.
Published: February 2023

Purpose:

To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era.

Methods:

Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak–associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum (“PXE” or “no PXE”) and between eyes previously treated or not with photodynamic therapy (“PDT” or “no PDT”).

Results:

Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47–175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively.

Conclusion:

Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.
MULTIMODAL RETINAL IMAGING REVEALS NEW PATHOGENIC INSIGHTS IN CENTRAL AREOLAR CHOROIDAL DYSTROPHY: A CASE SERIES
Authors: Romano Francesco , Cozzi Elisa , Boon Camiel J.F. , Staurenghi Giovanni , Salvetti Anna Paola
Published: February 2023

Purpose:

To describe novel imaging findings in a family affected by central areolar choroidal dystrophy.

Methods:

Case series with multimodal retinal imaging assessment.

Results:

A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium. Blue-light autofluorescence of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence. Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyperautofluorescent using blue-light autofluorescence and as hypoautofluorescent using near-infrared autofluorescence. Optical coherence tomography angiography revealed several tiny areas of flow voids in correspondence of the retinal pigment epithelium alterations of both eyes. Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of retinal pigment epithelium atrophy surrounded by yellowish deposits and a hypopigmented halo. Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of central areolar choroidal dystrophy.

Conclusion:

Multimodal imaging can reveal new pathogenic insights in central areolar choroidal dystrophy. Of notice, near-infrared autofluorescence and optical coherence tomography angiography are able to detect retinal pigment epithelium hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.
Hair Transplantation Complicated by Methicillin-resistant Staphylococcus Aureus Sepsis and Endogenous Endophthalmitis
Authors: Abraham Joseph R. , Singh Rishi P. , Srivastava Sunil K. , Mammo Danny A.
Published: February 2023

Purpose:

To describe a case of endogenous endophthalmitis as a complication from hair transplantation

Methods:

Case report of a 53-year-old male with history of recent hair transplantation

Results:

The patient presented with a febrile illness and blurry vision one week after hair transplantation. Infectious workup included blood cultures positive for Methicillin-resistant Staphylococcus aureus and he was treated with intravenous antibiotics. Initial ocular exam demonstrated 20/30 and hand motions in the right and left eyes, respectively, with significant vitritis. He underwent vitreous tap and injections of vancomycin and dexamethasone in both eyes and removal of purulent staple from site of recently transplanted hair. His ocular and systemic symptoms improved. Approximately 3 months after initial clearing of the initial infection he had recurrence of bacteremia that prompted repeat intravitreal and systemic antibiotics. His vision returned to baseline with mild residual optic nerve pallor and atrophic retinal changes in the left eye.

Conclusion:

Hair transplantation is associated with minimal systemic complications, but in rare cases, sepsis is possible and can result in intraocular seeding causing endophthalmitis. MRSA endogenous endophthalmitis frequently results in negative vitreous taps and treatment outcomes in the literature have been shown to vary widely including a return to baseline vision as in the described case.
Kearns-Sayre Syndrome Masquerading as Myasthenia Gravis
Authors: Sokol Jared T. , Hoyek Sandra , Fulton Anne B. , Patel Nimesh A.
Published: February 2023

Purpose:

Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion syndrome that is characterized by the triad of onset commonly before age twenty, pigmentary retinopathy, and chronic progressive external ophthalmoplegia. Here we present a case of KSS masquerading as myasthenia gravis (MG).

Methods:

Case report.

Results:

A 15-year-old male with a presumed diagnosis of MG presented with blurry vision, ophthalmoplegia, and ptosis. He was found to have a mitochondrial pigmentary retinopathy and was eventually diagnosed with KSS after mtDNA sequencing revealed a novel large-scale deletion of 7.9kb of mtDNA from nucleotides 6578 to 14,460.

Conclusions:

We report a case of KSS found to have a novel large-scale mtDNA deletion. The presence of a mitochondrial pigmentary retinopathy found on dilated examination led to reconsideration of the previous diagnosis of MG and ultimately led to the correct diagnosis of KSS.
Monkeypox-Associated Disciform Keratitis
Authors: Alsarhani Waleed K. , Chan Clara C. , Boyd Shelley R. , Hasso Maan , Almeer Ahmed , Tan Darrell H. S.
Published: February 2023

Purpose:

The purpose of this study was to describe a case of monkeypox (MPX)-associated disciform keratitis.

Methods:

This is a case report.

Results:

A 36-year-old male patient presented to the infectious diseases clinic with a 1-week history of disseminated pustular skin lesions, a 4-day history of constitutional symptoms, and redness in the left eye. Testing of blood, 2 skin lesions, and a conjunctival swab confirmed the presence of MPX virus by polymerase chain reaction. On ophthalmologic examination on the 17th day of illness, there was a corneal epithelial ridge that stained with fluorescein with disciform corneal edema and underlying keratic precipitates. The patient was treated with oral tecovirimat 600 mg twice a day for 14 days and topical prednisolone acetate 1% 4 times daily, starting 2 days later. On completion of oral treatment, his corneal findings had resolved except for a small subepithelial scar at which time topical steroids were tapered.

Conclusions:

MPX may cause disciform keratitis and scarring that closely resembles other ocular viral infections. Clinical trials are urgently needed to define the optimal management of human MPX infections and reduce vision loss.
Age-Related Changes in Corneal Sensitivity
Authors: Nosch Daniela S. , Käser Emanuele , Bracher Tobias , Joos Roland E.
Published: February 2023

Purpose:

The aim of this prospective cross-sectional cohort study was to clinically test whether corneal sensation decreases with age, based on subject feedback (psychophysical method), and whether it correlates with general pain perception.

Methods:

Subjects were recruited from 2 equally large age groups: group A (18–30 years) and group B (50–70 years; n = 45 per group). The inclusion criteria were healthy eyes, Ocular Surface Disease Index ≤13, and no contact lens wear. Corneal sensitivity threshold (CST) measurements were performed twice during each of the 2 visits, with the aid of the new Swiss liquid jet esthesiometer for corneal sensitivity (SLACS) and Cochet–Bonnet (CB) esthesiometer. A general pain sensitivity score was obtained from all participants.

Results:

Ninety subjects completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). Statistically higher CSTs for age group B were only observed for SLACS (mean difference: 1.58 dB, P < 0.001). No correlation was observed between the pain score and the CSTs obtained with either esthesiometry method (r = 0.11, P = 0.25 for liquid jet and r=−0.076, P = 0.61 CB).

Conclusions:

A statistically significant decrease in corneal sensitivity was observed for the older age group with SLACS in this study, with CB however only a trend in the same direction was noted. General pain perception was not found to correlate with ocular surface sensation.
Comparison of Corneal Biomechanics Treated With Femtosecond Laser-Assisted In Situ Keratomileusis and Small-Incision Lenticule Extraction by New Corneal Biomechanical Parameters of Corvis ST II
Authors: Liu Mingna , Li Na , Chen Tong , Tian Ge , Lin Yue , Gao Hua , Shi Weiyun
Published: February 2023

Purpose:

The aim of this study was to compare corneal biomechanics treated with femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE) for myopia and astigmatism using the new corneal biomechanical parameters of Corvis ST II.

Methods:

This was a prospective nonrandomized controlled study. Patients treated with FS-LASIK or SMILE between January 2018 and July 2018 were included. Corvis ST II was performed to measure corneal biomechanical parameters, including deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm), integrated inverse radius (Integr Radius), stiffness parameter at first applanation (SP-A1), and Ambrosio relational thickness through the horizontal meridian (ARTh), preoperatively, 1 month postoperatively, and 6 months postoperatively. Pentacam pachymetry was used to assess the reduction in pachymetry.

Results:

Forty-five eyes underwent FS-LASIK, and 45 eyes underwent SMILE. The new parameters obtained by Corvis ST II between preoperative and postoperative measurements showed significant changes after FS-LASIK or SMILE (all P < 0.001). Postoperative SP-A1 significantly decreased in the 2 groups (108.88 ± 14.47–73.32 ± 13.2 in FS-LASIK and 105.79 ± 17.68–73.91 ± 14.81 in SMILE). Eyes with equal preoperative pachymetry, intraocular pressure, and spherical equivalents showed no significant differences in these new parameters measured using Corvis ST II (all P > 0.05) between the 2 groups. The prediction of the laser platform overestimated the measured pachymetry reduction in the SMILE group (111.93 ± 15.18 μm vs. 87.16 ± 15.47 μm).

Conclusions:

New corneal biomechanical parameters measured using Corvis ST II showed no significant differences between FS-LASIK and SMILE in eyes with homogeneous preoperative parameters. The laser software platform may have overestimated the actual corneal reduction in the eyes treated with SMILE.
Novel Treatments for Chronic Ocular Surface Pain
Authors: Mangwani-Mordani Simran , Goodman Courtney F. , Galor Anat
Published: February 2023

Several etiologies can contribute to ocular surface pain including nociceptive, peripheral neuropathic, and central neuropathic mechanisms. Clinical clues can help identify contributors to ocular surface pain in a patient. In individuals whose pain persists despite targeting nociceptive contributors, neuropathic mechanisms should be considered and addressed using oral, topical, and/or adjuvant agents.
BRAF Immunohistochemical Studies of Pediatric Conjunctival Lesions
Authors: Chen Kelsey , McInnis-Smith Kerri , Tiwari Nishant , Moser Justin C. , Ramasubramanian Aparna
Published: February 2023

Purpose:

The purpose of this study was to analyze the prevalence of an activating mutation in the B-Raf proto-oncogene (BRAF) V600E immunoreactivity in pediatric conjunctival lesions.

Methods:

This retrospective case–control study included 32 pediatric patients who underwent surgical excision of conjunctival lesions between Jan 2019 and May 2022. The collected data included demographic data, clinical features, and histopathologic characteristics of the lesion, including BRAF V600E positivity. The Student t test and the Fisher exact test were used to determine the significance of the associations between clinical variables and BRAF positivity.

Results:

BRAF immunoreactivity was positive in 11/32 lesions (34%). Age at diagnosis did not correlate with BRAF positivity, with a mean age at diagnosis of 131.7 months for patients with BRAF+ lesions and 134.7 months for those with BRAF− lesions (P > 0.1). No clinical or pathological features were found to be significantly correlated with BRAF positivity, although there was a trend toward BRAF positivity in the presence of cysts (P = 0.072).

Conclusions:

BRAF reactivity was present in approximately one-third of pediatric conjunctival nevi but does not correlate significantly with unique clinical or histopathological features.
Establishing a Virtual Corneal Clinic: A Real-Time Teleophthalmology Approach
Authors: Siregar Sharita Rosalyne , Ardiani Lily Silva , Chua Anna , Chong Berlisa Yong Qin , Tan Donald Tiang Hwee
Published: February 2023

Purpose:

Keratoplasty patients require regular and timely follow-ups. During this COVID-19 pandemic which restricted global travel, we developed a novel real-time, hybrid teleophthalmology approach to comanage international keratoplasty patients between Singapore and Indonesia.

Methods:

A retrospective consecutive observational study of 72 corneal patients (63 were postkeratoplasty) who attended a virtual corneal clinic (VCC) between June 2020 and April 2021 at JEC Eye Hospitals (JEC) in Jakarta, Indonesia. ZOOM Meeting software (Zoom Video Communication Inc, San Jose, CA) was used to simultaneously connect the Singapore corneal specialist at Eye & Cornea Surgeons (ECS), Singapore, using a real-time approach. Clinical examinations included full panels of video-linked corneal, glaucoma, and retinal imaging and investigations performed before real-time video-linked slit-lamp examination, with immediate clinical decision making between corneal specialists and patients.

Results:

VCC enabled effective real-time clinical evaluation and collaborative clinical decisions, with full patient interaction, with the aim of maintenance of graft clarity, visual function, and management of comorbidities—a) topical and systemic medications were adjusted in 79.2% of patients; b) further referrals to glaucoma, retinal, and oculoplastic subspecialists were made in 16.6% of cases; c) additional adjunctive surgical procedures were performed at JEC in 6.9% cases; and d) government permission was obtained for 4 patients (5.6%) to fly to Singapore for urgent corneal surgery.

Conclusions:

The virtual corneal clinic is a novel real-time hybrid teleophthalmology approach which is effective in the comanagement of international keratoplasty patients and represents the advances in ophthalmic telemedicine.
Artificial intelligence in glaucoma: posterior segment optical coherence tomography
Authors: Gutierrez Alfredo , Chen Teresa C.
Published: February 2023

Purpose of Review

To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging.

Recent Findings

DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed.

DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54).
Agreement of a Novel Artificial Intelligence Software With Optical Coherence Tomography and Manual Grading of the Optic Disc in Glaucoma
Authors: Shroff Sujani , Rao Divya P. , Savoy Florian M. , Shruthi S. , Hsu Chao-Kai , Pradhan Zia S. , Jayasree P.V. , Sivaraman Anand , Sengupta Sabyasachi , Shetty Rohit , Rao Harsha L.
Published: February 2023

Précis:

The offline artificial intelligence (AI) on a smartphone-based fundus camera shows good agreement and correlation with the vertical cup-to-disc ratio (vCDR) from the spectral-domain optical coherence tomography (SD-OCT) and manual grading by experts.

Purpose:

The purpose of this study is to assess the agreement of vCDR measured by a new AI software from optic disc images obtained using a validated smartphone-based imaging device, with SD-OCT vCDR measurements, and manual grading by experts on a stereoscopic fundus camera.

Methods:

In a prospective, cross-sectional study, participants above 18 years (Glaucoma and normal) underwent a dilated fundus evaluation, followed by optic disc imaging including a 42-degree monoscopic disc-centered image (Remidio NM-FOP-10), a 30-degree stereoscopic disc-centered image (Kowa nonmyd WX-3D desktop fundus camera), and disc analysis (Cirrus SD-OCT). Remidio FOP images were analyzed for vCDR using the new AI software, and Kowa stereoscopic images were manually graded by 3 fellowship-trained glaucoma specialists.

Results:

We included 473 eyes of 244 participants. The vCDR values from the new AI software showed strong agreement with SD-OCT measurements [95% limits of agreement (LoA)=−0.13 to 0.16]. The agreement with SD-OCT was marginally better in eyes with higher vCDR (95% LoA=−0.15 to 0.12 for vCDR>0.8). Interclass correlation coefficient was 0.90 (95% CI, 0.88–0.91). The vCDR values from AI software showed a good correlation with the manual segmentation by experts (interclass correlation coefficient=0.89, 95% CI, 0.87–0.91) on stereoscopic images (95% LoA=−0.18 to 0.11) with agreement better for eyes with vCDR>0.8 (LoA=−0.12 to 0.08).

Conclusions:

The new AI software vCDR measurements had an excellent agreement and correlation with the SD-OCT and manual grading. The ability of the Medios AI to work offline, without requiring cloud-based inferencing, is an added advantage.