Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus.

Background: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. Methods: We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. Results: For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/µl), neutrophils (6.01 × 103 cells/µl), lymphocytes (12.98 × 103 cells/µl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/µl), neutrophils (6.58 × 103 cells/µl), lymphocytes (16.64 × 103 cells/µl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. Conclusion: In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

A Case of a Bumpy Retina.

A 77-year-old male had 3 months of progressive vision decline in the left eye. Dilated fundus examination revealed diffuse hyperpigmented lesions involving the macula and superior fundus that corresponded to areas of nodular retinal pigment epithelium thickening on optical coherence tomography. What would you do next?

Visual Acuity Outcomes and Complications after Intraocular Lens Exchange: An IRIS® Registry (Intelligent Research in Sight) Analysis.

PURPOSE: To assess risk factors for worse visual acuity (VA) outcomes after intraocular lens (IOL) exchange, and the most common postsurgical complications. DESIGN: Retrospective cohort study. PARTICIPANTS: Eyes from patients 18 years of age and older in the IRIS® Registry (Intelligent Research in Sight) that underwent IOL exchange in the United States between 2013 and 2019. METHODS: Vision improvement compared with baseline was determined at 1 year after surgery. A multivariable generalized estimating equation model adjusting for demographic factors and baseline vision was used to identify factors associated with VA worse than 20/40 at 1 year. MAIN OUTCOME MEASURES: Visual outcomes and postoperative complications after lens exchange. RESULTS: A total of 46 063 procedures (n = 41 925 unique patients) were included in the analysis. Overall, VA improved from a mean ± standard deviation (SD) of 0.53 ± 0.58 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/70) before surgery to a mean ± SD of 0.31 ± 0.40 logMAR (Snellen equivalent, 20/40) at 1 year. Among eyes with VA recorded at both baseline and 1 year after surgery, 60.5% achieved VA of 20/40 or better at 1 year. Vision of worse than 20/40 at 1 year was associated with greater age (odds ratio [OR], 1.16 per 5-year increase; 95% confidence interval [CI], 1.14-1.18) and higher logMAR baseline VA (OR, 1.14 per 0.1-logMAR increase; 95% CI, 1.14-1.15), as well as Black or African American (OR, 1.96; 95% CI, 1.68-2.28), Hispanic (OR, 1.82; 95% CI, 1.59-2.08), and Asian (OR, 1.48; 95% CI, 1.21-1.81) race or ethnicity versus White race, Medicaid (OR, 1.78; 95% CI, 1.40-2.25) versus private insurance, smoking history (OR, 1.22; 95% CI, 1.11-1.35), and concurrent anterior (OR, 1.65; 95% CI, 1.51-1.81) and posterior (OR, 1.53; 95% CI, 1.41-1.66) vitrectomy versus no vitrectomy. Female sex was associated with better VA at 1 year. At 1 year, epiretinal membrane (10.9%), mechanical lens complication (9.4%), and dislocation of the replacement lens (7.1%) were the most common complications. CONCLUSIONS: In this large national cohort, the annual number of IOL exchanges rose steadily over time. Vision improved in 60.2% of patients; worse visual outcomes were associated with greater age, worse baseline vision, Black race, Hispanic ethnicity, Medicaid insurance, smoking, and concurrent vitrectomy. Epiretinal membrane was the most common complication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Endophthalmitis rates and risk factors following intraocular surgeries in the medicare population from 2016 to 2019.

AIMS: To determine endophthalmitis rates and risk factors following intraocular surgeries in the Medicare population. METHODS: Retrospective, cross-sectional study from 2016 to 2019 in Medicare fee-for-service and Medicare Advantage beneficiaries. 100% Medicare claims were used to identify eyes that underwent intraocular surgery. Exclusion criteria included eyes that had intraocular surgery 42 days before or after and eyes in patients with a history of endophthalmitis within 12 months. RESULTS: 9 744 400 intraocular surgeries were performed among Medicare beneficiaries from 2016 to 2019. A 42-day postoperative endophthalmitis rate was 0.09%. Endophthalmitis rate by surgery type was 0.43% for corneal transplant, 0.36% for secondary intraocular lens (IOL), 0.24% for retina, 0.16% for glaucoma, 0.11% for cataract combined with other procedures and 0.08% for cataract surgeries alone. On multivariable analysis, the risk of endophthalmitis was increased for all intraocular surgery types when compared with cataract surgeries; adjusted OR (aOR) 5.30 (p<0.01) for corneal transplant, aOR 4.50 (p<0.01) for secondary IOL, aOR 3.00 (p<0.01) for retina, aOR 1.93 (p<0.01) for glaucoma, aOR 1.45 (p<0.01) for combined cataract surgeries. Increased risk of developing endophthalmitis was associated with older age (≥85 vs 65-75 years: aOR 1.36; p<0.01), male sex (aOR 1.20; p<0.001) and greater Charlson Comorbidity Index (≥7 vs 0: aOR 1.79; p<0.01). CONCLUSIONS: Postoperative endophthalmitis rate after intraocular surgeries was 0.09% between 2016 and 2019 for Medicare beneficiaries. Endophthalmitis rates were highest for corneal transplant surgeries followed by secondary IOL surgeries and lowest for cataract surgeries. Older age, male gender and higher comorbidity index were associated with risk of endophthalmitis.

Accuracy of swept source biometry device in detecting macular diseases compared with swept source OCT.

OBJECTIVE: To assess the diagnostic accuracy of the IOLMaster 700 foveal scans to detect foveal pathology compared with a standard swept-source optical coherence tomography (SS-OCT) device. RESULTS: One hundred seventy eye scans of 95 patients were included in the final analyses. Ninety-nine (58.2%) scans were classified as abnormal by SS-OCT. Mean sensitivity of the biometry device was 67.5% (range: 51-84%) and mean specificity was 69.5% (range: 44-95%). Intra-class correlation coefficients were 0.912 and 0.835, for reader 1 and 2, respectively. Area under the curve for receiver operating curve was 0.726. Foveal scans of the IOLMaster 700 can provide clinically useful information. Clinicians should pay attention to the macular scans when reviewing biometry prior to cataract surgery and standard macular OCT should ideally be supplemented in suspicious cases.

Hybrid Deep Learning Techniques for Securing Bioluminescent Interfaces in Internet of Bio Nano Things.

The Internet of bio-nano things (IoBNT) is an emerging paradigm employing nanoscale (~1-100 nm) biological transceivers to collect in vivo signaling information from the human body and communicate it to healthcare providers over the Internet. Bio-nano-things (BNT) offer external actuation of in-body molecular communication (MC) for targeted drug delivery to otherwise inaccessible parts of the human tissue. BNTs are inter-connected using chemical diffusion channels, forming an in vivo bio-nano network, connected to an external ex vivo environment such as the Internet using bio-cyber interfaces. Bio-luminescent bio-cyber interfacing (BBI) has proven to be promising in realizing IoBNT systems due to their non-obtrusive and low-cost implementation. BBI security, however, is a key concern during practical implementation since Internet connectivity exposes the interfaces to external threat vectors, and accurate classification of anomalous BBI traffic patterns is required to offer mitigation. However, parameter complexity and underlying intricate correlations among BBI traffic characteristics limit the use of existing machine-learning (ML) based anomaly detection methods typically requiring hand-crafted feature designing. To this end, the present work investigates the employment of deep learning (DL) algorithms allowing dynamic and scalable feature engineering to discriminate between normal and anomalous BBI traffic. During extensive validation using singular and multi-dimensional models on the generated dataset, our hybrid convolutional and recurrent ensemble (CNN + LSTM) reported an accuracy of approximately ~93.51% over other deep and shallow structures. Furthermore, employing a hybrid DL network allowed automated extraction of normal as well as temporal features in BBI data, eliminating manual selection and crafting of input features for accurate prediction. Finally, we recommend deployment primitives of the extracted optimal classifier in conventional intrusion detection systems as well as evolving non-Von Neumann architectures for real-time anomaly detection.

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan.

Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.

Management of Severe Hemophilia A: Low-Dose Prophylaxis vs. On-Demand Treatment.

INTRODUCTION: Prophylactic clotting factor infusion regimens to prevent bleeding and joint deformity has become the standard of care in severe hemophilia A patients. AIM: To assess low-dose factor prophylaxis in our population as an alternative approach to managing severe hemophilia A. METHODS: A prospective cohort study that included 68 hemophilia A patients divided into two groups, i.e., Prophylaxis and on-demand. The two groups were compared for annualized bleeding rate (ABR), hospitalization, units of factor VIII (FVIII) infused, or plasma products transfused, i.e., fresh frozen plasma (FFP) and cryoprecipitate (CP), and development of FVIII inhibitors. RESULTS: Of the 68 patients recruited in this study, 25 (36.7%) were in the prophylaxis group, and 43(63.3%) were in the on-demand group. The on-demand group presented a higher median-IQR ABR [8(20-3) vs. 5(10-1.5), p-value 0.024], several hospitalizations (39.7% vs. 0, p-value 0.001), and inhibitor development (9.3% vs. 0, p-value 0.289) compared to the prophylaxis group. The prophylaxis approach demonstrated a significant negative correlation of ABR with FVIII prophylaxis (r=-0484, p=value=0.014). Moreover, no hospitalizations or inhibitor development was observed in the prophylaxis group. The estimated annual consumption of FVIII was 328 IU/kg/year in the on-demand group and 1662.6 IU/kg/year in the prophylaxis group. However, a highly significant difference in plasma product utilization was observed between the two groups, i.e., p-value <0.001 and 0.038 for FFP and CP, respectively. CONCLUSION: Low-dose factor prophylaxis resulted in improved outcomes compared to on-demand treatment in terms of ABR, joint bleeding, hospitalization, and the development of inhibitors. This treatment approach should be adopted as an economically feasible alternative to high-dose Prophylaxis in resource-constrained countries.

Reticulated Platelet Count as a Diagnostic Tool in Immune Thrombocytopenia (ITP).

OBJECTIVE: This study aimed to compare the reticulated platelet count between patients having thrombocytopenia secondary to autoimmune destruction (immune thrombocytopenia {ITP}), bone marrow failure, and healthy controls who presented to a tertiary care hospital in Karachi, Pakistan. METHODOLOGY: A cross-sectional study was conducted from February 2021 to October 2022 in the Department of Hematology, National Institute of Blood Disease (NIBD) Hospital in Karachi, Pakistan, that involved examining three groups: 30 patients with immune thrombocytopenia, 30 patients with thrombocytopenia secondary to reduced production from bone marrow, and 30 healthy controls. The study utilized the Sysmex XN-1000 (Hyogo, Japan: Sysmex Corporation) automated hematology analyzer to perform a complete blood count (CBC) test. Additionally, peripheral blood was stained with Leishman stain and examined under a microscope to eliminate pseudo thrombocytopenia and identify any abnormal cells or dysplasia. The immature platelet fraction (IPF) was then performed on Sysmex XN 1000 after ensuring adequate quality control. Finally, the data were analyzed using DATAtab (Graz, Austria: DATAtab) and SPSS version 25 (Armonk, NY: IBM Corp.). RESULTS: Of the ninety participants, the median age was 33 years with a range of 18-71 years. Patients with ITP had a significantly higher median IPF% (median=26.65, IQR=15-39.4) than thrombocytopenia due to bone marrow failure (median=9.25, IQR=4.55-14.30) and healthy controls (median=7, IQR=4.40-9.90), with a p-value of 0.001. The immune thrombocytopenia group demonstrated an increase in IPF% as platelet counts increased, indicating a significant moderate correlation between IPF% and platelets in these patients (r=0.438, p=0.016) and confirming that IPF% was an independent predictor for the detection of ITP. CONCLUSION: Reticulated platelet count may be a useful diagnostic tool to differentiate between ITP and thrombocytopenia caused by bone marrow failure. Because of its non-invasive nature, IPF is a valuable tool for expediting the management of thrombocytopenia associated with increased IPF.

Sex and Racial and Ethnic Diversity Among Ophthalmology Subspecialty Fellowship Applicants.

Importance: Physician-patient concordance in sex and race is associated with improved patient outcomes. Studies have explored diversity among ophthalmology residents and faculty, but to our knowledge, not among ophthalmology fellows. Objective: To assess diversity by sex and race and ethnicity among fellowship applicants in ophthalmology subspecialties and compare match rates by applicants' sex and underrepresented in medicine (URiM) status. Design, Setting, and Participants: This cohort study examined ophthalmology subspecialty fellowship data from the 2021 San Francisco Match. Main Outcomes and Measures: Applicant characteristics were stratified by sex and URiM status and compared using χ2, Mann-Whitney U, and median tests. For applicants who matched, the percentages of female and URiM applicants were compared among the ophthalmic subspecialties. A multivariable logistic regression model was used to assess the association of applicant characteristics with their match outcomes. Results: Included in the sample were 537 candidates who applied for an ophthalmology fellowship using the 2021 San Francisco Match; 224 applicants (42.6%) were female, and 60 applicants (12.9%) had URiM status. Females and males had similar match rates (70.5% [n = 158] and 69.2% [n = 209], respectively; P = .74), but females had a higher median (IQR) US Medical Licensing Examination (USMLE) Step 2 Clinical Knowledge (CK) score (248 [240-258] vs 245 [234-254]; P = .01). The pediatric ophthalmology subspecialty had the highest percentage of female matched applicants (67.5%; 27 of 40 matched applicants), while the retina subspecialty had the highest percentage of males (68.9%; 84 of 122 matched applicants). URiM applicants had lower match rates (55.0%, n = 33) than non-URiM applicants (72.2%, n = 293; P = .007). The URiM applicants had lower median (IQR) scores on the USMLE Step 1 (238 [227-247]) compared with Asian applicants (246 [235-254]) and White applicants (243 [231-252]; P = .04). Additionally, URIM applicants submitted fewer median (IQR) applications (10 [1-23]) than Asian (21 [8-37]) and White (17 [8-32]; P = .001) applicants and completed fewer interviews (median [IQR], 2 [0-11]) than Asian (median [IQR], 12 [3-18]) and White applicants (median [IQR], 8 [1-14]; P = .001). Among matched fellows in each subspecialty, URiM applicants comprised 13.9% (n = 11) in glaucoma, 10% (n = 4) in pediatric ophthalmology, 7.3% (n = 6) in cornea, and 6.6% (n = 8) in retina. Conclusions and Relevance: Ophthalmology subspecialty fellowship match rates were lower for URiM vs non-URiM applicants in 2021. Underrepresentation of females exists in the retina subspecialty, while racial and ethnic differences exist in all ophthalmology subspecialty fellowships examined. Monitoring trends in fellowship diversity over time should help inform where targeted efforts could improve diversity.

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Importance: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups. Objective: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes. Design, Setting, and Participants: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and December 31, 2012, were identified. Data were then extracted on incident systemic adverse events among this patient cohort from January 1, 2013, to December 31, 2017. All individuals with diabetes who did and did not receive anti-VEGF injections were included. Patients with a history of prior systemic adverse events and those who received an intravitreal injection between January 1, 2011, and December 31, 2012, were excluded. Data were analyzed from October 2019 to March 2023. Exposure: Anti-VEGF injection. Main Outcomes and Measures: Proportion of patients with any incident systemic adverse event, acute myocardial infarction, cardiovascular disease, or kidney disease at 1-, 3-, and 5-year follow-up. Results: A total of 1 731 782 patients (mean [SD] age, 63.8 [12.3] years; 1 656 589 [95.7%] male) with type 2 diabetes were included. DR was present in 476 013 (27.5%), and 14 022 (0.8%) received anti-VEGF injections. Of the total number of patients with type 2 diabetes, 321 940 (18.6%) developed systemic adverse events between 2013 and 2017. The 5-year cumulative incidence of any systemic adverse event was 37.0% (5187/14 022) in the injection group vs 18.4% (316 753/1 717 760) in the noninjection group (P < .001). Anti-VEGF injections were independently associated with a higher likelihood of developing any systemic adverse event (odds ratio, 1.8; 95% CI, 1.7-1.9) when controlling for age, race, sex, ethnicity, tobacco use, severity of DR, Deyo-Charlson Comorbidity Index score, mean hemoglobin A1c, total number of injections, and statin use. Conclusion and Relevance: In this study, intravitreal anti-VEGF injections were independently associated with a higher likelihood of systemic adverse events among patients with diabetes.

Open-Globe Injury Repairs in the American Academy of Ophthalmology IRIS® Registry 2014 - 2018: Incidence, Risk Factors, and Visual Outcomes.

PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95% CI, 1.6-1.8), and South (OR, 1.4; 95% CI, 1.3-1.5) and West (OR, 1.3; 95% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA < 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95% CI, 8.0-15.7), older age (e.g., > 80 years vs. < 21 years; OR, 5.8; 95% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study.

BACKGROUND/AIMS: Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness. METHODS: Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c. RESULTS: 7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI -1.28 µm to -0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI -1.17 µm to -0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor. CONCLUSION: Superior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes.

SYPHILITIC OUTER RETINOPATHY: A MASQUERADING DIAGNOSIS REVEALED AFTER STEROID-INDUCED PROGRESSION TO PANUVEITIS.

PURPOSE: To report a case of syphilitic outer retinopathy revealed after progression to panuveitis after a course of oral steroids for suspected poison ivy. METHODS: Retrospective case report. RESULTS: A 44-year-old diabetic man presented with progressive symptoms of nyctalopia and color vision changes associated with outer retinal disruption on macular imaging but minimal evidence of intraocular inflammation on examination. A short course of oral steroids for an unrelated skin condition induced rapid progression to frank panuveitis with retinal vascular sheathing and retinal whitening. Systemic workup identified syphilis as the etiology. The patient's visual symptoms and disruption of the photoreceptor and retinal pigment epithelial layers on OCT improved after treatment with IV penicillin. CONCLUSION: Syphilitic outer retinopathy represents an unusual manifestation of ocular syphilis that can present with minimal examination findings. We present here a case of oral steroid use resulting in the progression of syphilitic outer retinopathy to a more fulminant form of syphilitic uveitis that ultimately revealed the correct diagnosis and prompted the correct intervention. This case highlights the importance of maintaining a high level of suspicion for this treatable condition.

Predictors of matching into an ophthalmology fellowship for international medical graduates: a San Francisco match analysis.

PURPOSE: To describe the characteristics and outcomes of international medical graduates (IMGs) applying for ophthalmology fellowship match. METHODS: Design Case control study. Setting San Francisco Fellowship Match data between 2010 and 2017. Participants IMGs applying for ophthalmology fellowships. Main outcome(s) and measure(s) Applicant characteristics for IMGs were stratified by their match outcome and compared using Chi-Square and Mann-Whitney U test. A multivariable logistic regression model was used to assess the effect of applicant characteristics on their match outcomes. RESULTS: 22.62% (785/3471) of the fellowship match applicants were IMGs of which 35.92% (n = 282) matched. This rate was 58% lower than the 86.4% match rate for US-MG (p < 0.001). Factors associated with higher odds of matching among IMGs were graduating from a US residency (Odds Ratio (OR):2.330; 95% Confidence Interval (CI):1.433-3.789), higher USMLE Step 3 score (OR:1.019; 95% CI: 1.006-1.032), applying to more programs (OR:1.035; 95% CI: 1.017-1.053), ranking more programs (OR:1.200; 95% CI: 1.096-1.313) and having a higher percentage of programs ranked (OR:1.021; 95% CI: 1.014-1.028). CONCLUSIONS: Fellowship match rates for IMGs were significantly lower than for US-MGs. IMGs graduating from an ophthalmology residency in the US, scoring higher Step 3 scores, distributing more applications, and ranking more programs had increased odds of matching. This information may assist IMG fellowship applicants and their mentors when they consider pursuing an ophthalmology fellowship program in the US.

Frequency Of CD34 Expression In Acute Lymphoblastic Leukaemia And Its Correlation With Clinicopathological Characteristics: A Single Centre Experience From Pakistan.

Background: This study was carried out to determine the frequency of CD34 positivity in acute lymphoblastic leukaemia (B-ALL) in our population and to report its association with the clinicopathological profile at the time of diagnosis. Methods: The cross-sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from March 2020 till December 2020.Newly diagnosed patients were selected, from both genders and all age groups. Relevant history and findings of physical examination were recorded. Immunohistochemistry was done on trephine biopsy and molecular studies were carried on bone marrow aspirates or peripheral blood samples. Results: Out of 105 patients enrolled, 67 (63.8%) were males, with a male to female ratio (M: F) 1.8:1. Of the total patients, 62 (59.04%) were above 15 years of age. CD34 was expressed in 73 (69.5%) cases. Lymphadenopathy, splenomegaly, and hepatomegaly were separately noted in context to CD 34 expression in 22 (66.6%), 24 (64.8%), and 14 (58.3%) patients, respectively. CNS disease was seen in a total of 3(2.75%) subjects, in which 2 (66.6%) of the patients had CD34 expression. Total 81 patients in our study fall into the high-risk group out of which CD 34 expression was seen in 58(71.6%) subjects. Cytogenetic analysis, BCR-ABL p190, and MLL gene rearrangement were investigated in all participants. Cytogenetic analysis revealed an abnormality in 20 (19%) cases out of which 13 (17.8%) cases were from CD34 positive group. Conclusion: Our study reported CD34 expression in more than two-thirds of cases. High-risk disease was significantly associated with CD34 expression.

The Outcome of Hodgkin Lymphoma With Reference to Prognostic Markers.

OBJECTIVES: This study aimed to determine the impact of prognostic markers on the outcomes of Hodgkin lymphoma. METHODS: It is a cross-sectional, single-center study. A total of 60 patients diagnosed with Hodgkin lymphoma were recruited for the study over five years between 2016 to 2020. The study setting was the National Institute of Blood and Bone Marrow Transplant in Pakistan. The Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. RESULTS: In the study population, 63.3% of the patients were male (38/60), and 36.7% were female (22/60). Hodgkin lymphoma was divided into four stages: stage I (18.3%), stage II (18.3%), stage III (46.7%), and stage IV (16.7%). Patients in stage III had a higher value of hemoglobin (Hb) than in other stages of the disease. The erythrocyte sedimentation rate was high in 56.7% of stage III patients than in patients of the other stages. The lactate dehydrogenase (LDH) levels were not under the normal range in 51.6% of patients. Only 20% of patients in stage III had LDH values within the normal range, whereas 26.6% did not. CONCLUSION: There was a significant impact of prognostic factors on the survival of patients with Hodgkin lymphoma.

Effect of pupil dilation on IOLMaster® measurements in Pakistani Eyes.

Objectives: To analyse the effect of pupil dilation on intraocular lens instrument IOLMaster 500 biometric measurements, and to determine the effect of these measurements on intraocular lens power calculations in Asian eyes. METHODS: The prospective study was conducted at the Aga Khan University Hospital, Karachi, between January and April 2017, and comprised all patients scheduled for cataract surgery who underwent scanning with IOLMaster 500. For each patient, pre-dilation and post-dilation measurements were taken. The intraocular lens power was determined through Sanders/Retzlaff/Kraff Theoretical, Holladay, and Hoffer Q formulae. Data was analysed using SPSS 24. RESULTS: There were 276 eyes of 138 participants who had a mean age of 59.7±11.1 years. Anterior chamber depth changed significantly with pupil dilation (p=0.001). No significant changes were observed in the axial length (p=0.410), keratometry measurements (p=0.931), and intraocular lens power calculations (p>0.05). CONCLUSIONS: The change in anterior chamber depth, though significant, was perhaps clinically non-significant.

Experimental Study of Potential CD8+ Trivalent Synthetic Peptides for Liver Cancer Vaccine Development Using Sprague Dawley Rat Models.

Background: Liver cancer (LC) is the most devastating disease affecting a large set of populations in the world. The mortality due to LC is escalating, indicating the lack of effective therapeutic options. Immunotherapeutic agents may play an important role against cancer cells. As immune cells, especially T lymphocytes, which are part of cancer immunology, the design of vaccine candidates for cytotoxic T lymphocytes may be an effective strategy for curing liver cancer. Results: In our study, based on an immunoinformatics approach, we predicted potential T cell epitopes of MHC class I molecules using integrated steps of data retrieval, screening of antigenic proteins, functional analysis, peptide synthesis, and experimental in vivo investigations. We predicted the binding affinity of epitopes LLECADDRADLAKY, VSEHRIQDKDGLFY, and EYILSLEELVNGMY of LC membrane-bounded extracellular proteins including butyrophilin-like protein-2 (BTNL2), glypican-3 (GPC3), and serum albumin (ALB), respectively, with MHC class I molecules (allele: HLA-A∗01:01). These T cell epitopes rely on the level of their binding energy and antigenic properties. We designed and constructed a trivalent immunogenic model by conjugating these epitopes with linkers to activate cytotoxic T cells. For validation, the nonspecific hematological assays showed a significant rise in the count of white blood cells (5 × 109/l), lymphocytes (13 × 109/l), and granulocytes (5 × 109/l) compared to the control after administration of trivalent peptides. Specific immunoassays including granzyme B and IgG ELISA exhibited the significant concentration of these effector molecules in blood serum, indicating the activity of cytotoxic T cells. Granzyme concentration increased to 1050 pg/ml at the second booster dose compared to the control (95 pg/ml), while the concentration of IgG raised to 6 g/l compared to the control (2 g/l). Conclusion: We concluded that a potential therapeutic trivalent vaccine can activate and modulate the immune system to cure liver cancer on the basis of significant outcomes of specific and nonspecific assays.