CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

PURPOSE: To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. METHODS: A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. RESULTS: Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). CONCLUSION: The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

Extensive Dynamics of Aneurysms and Long-term Prognosis in IRVAN Syndrome: A Case Series.

OBJECTIVES: To report the extensive dynamic clinical condition and long-term therapeutic prognosis in three cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome. METHODS: Retrospective, interventional case series. RESULTS: Data of the three IRVAN syndrome patients were retrospectively reviewed at study enrollment and during the follow-up period. The mean follow-up time was 60 months. All three patients manifested the typical characteristics of IRVAN syndrome with bilateral eye involvement. The good long-term visual acuity has been maintained after treatment. The aneurysms showed extensive dynamic changes and regressed mostly. CONCLUSION: IRVAN syndrome is a rare condition that may progress rapidly and cause severe vision loss without treatment. The photocoagulation is beneficial and should be performed in the early phase. The aneurysms presented extensive dynamic changes through multimodal imaging which suggested a migratory inflammatory process involving retinal arterioles.

Relationship between renal function and prognosis of Chinese proliferative diabetic retinopathy patients undergoing the first vitrectomy: protocol for a prospective cohort study.

INTRODUCTION: China has the largest number of adults with diabetes aged 20-79 years (116.4 million) in 2019. Due to the socioeconomic condition or a lack of awareness of diabetic complications, many adults with diabetes have proliferative diabetic retinopathy (PDR) or renal function impairment at their first visit to the clinic for a sudden loss of vision, and pars plana vitrectomy (PPV) is required for their treatment. Risk factors for the outcomes and complications of PPV surgery in PDR patients have been widely explored in many epidemiological studies and clinical trials. However, few prospective studies have analysed the association between renal function and surgical outcomes in PDR. METHODS AND ANALYSIS: This is a single-centre, prospective cohort study of PDR patients with type 2 diabetes mellitus who have definite indications for PPV surgery with or without renal function impairment. We will consecutively enrol PDR patients who meet the inclusion and exclusion criteria from November 2020 to December 2023. Each participant will be followed up for at least 6 months after surgery. Clinical data from medical records and vitreous fluid will be collected.Demographic characteristics and study outcomes will be summarised using descriptive statistics. The variation will be described and evaluated using the χ² test or Kruskal-Wallis test. Generalise additive mixed models will be used to explore the association between the renal profile and surgical outcomes including BCVA, and retinal and choroidal microvasculature/microstructure. Multivariate ordinal regression analysis will be used to detect the independent association between renal profile and BCVA changes, and smooth curve fitting will be employed to briefly present the tendency. ETHICS AND DISSEMINATION: The trial has received ethical approval from the West China Hospital of Sichuan University. Results of this trial will be disseminated through publication in peer-reviewed journals and presentations at local and international meetings. TRIAL REGISTRATION NUMBER: ChiCTR2000039698.

Efficacy and Safety of Anti-Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison.

Background: We aimed to evaluate the comparative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD). Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost <15 letters in BCVA, the mean change in central retinal thickness, and the number of injections within 12 months. Results: Twenty-seven trials including 10,484 participants and eighteen treatments were identified in the network meta-analysis. The aflibercept 2 mg bimonthly, ranibizumab 0.5 mg T&E, and brolucizumab 6 mg q12w/q8w regimens had better visual efficacy. Brolucizumab had absolute superiority in anatomical outcomes and a relative advantage of safety, as well as good performance of aflibercept 2 mg T&E. The proactive regimens had slightly better efficacy but a slightly increased number of injections versus the reactive regimen. Bevacizumab had a statistically non-significant trend toward a lower degree of efficacy and safety. Conclusion: The visual efficacy of four individual anti-VEGF drugs is comparable. Several statistically significant differences were observed considering special anti-VEGF regimens, suggesting that brolucizumab 6 mg q12w/q8w, aflibercept 2 mg bimonthly or T&E, and ranibizumab 0.5 mg T&E are the ideal anti-VEGF regimens for nAMD patients. In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit.

Epidemiology, Clinical Characteristics, and Visual Outcomes of Patients with Intraocular Foreign Bodies in Southwest China: A 10-Year Review.

INTRODUCTION: Intraocular foreign bodies (IOFBs) are a serious subset of open-globe injury that can result in visual loss. This study analyzed the epidemiology, clinical characteristics, and visual outcomes of patients with IOFBs in Southwest China. METHODS: This retrospective study comprised 1,176 patients with the primary diagnosis of IOFBs who resided in Sichuan Province over a 10-year period. All data were collected from medical records and analyzed statistically. RESULTS: The annual incidence for IOFBs was 0.14 per 100,000 (95% confidence interval 0.12-0.16 per 100,000) people in Southwest China. In that period, IOFBs accounted for 22.3% of all open-globe injuries. Working-age male patients accounted for 79.1% of all IOFBs patients and there had significant differences in age distributions between genders (p < 0.001). Metallic IOFBs were the most common (74.6%) IOFB, but there were significant differences in the materials of IOFBs between adults and children of different age-groups (p < 0.001). At discharge, 277 (23.6%) patients had increased visual acuity (VA) and 95 (8.0%) had no light perception. Initial VA <20/200 (odds ratio [OR], 5.5; p < 0.001), increasing wound size (OR, 1.3; p = 0.004), IOFBs in the posterior segment (OR, 2.6; p = 0.002) and existing complications (traumatic cataract, endophthalmitis, retinal detachment, or retinal break) were independent risk factors for final VA <20/200. CONCLUSION: The incidence of IOFBs in Southwest China differed from global statistics. Adults and children had different clinical characteristics. Thus, their prevention strategies should be different.

The Role of 68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Preoperative Lymph Node Staging in Intermediate/High Risk Patients With Prostate Cancer: A Diagnostic Meta-Analysis.

Purpose: To evaluate the accuracy of 68Ga-PSMA positron emission tomography/computerized tomography (PET/CT) for preoperative lymph node staging using histopathological results of pelvic lymph node dissection (PLND) as reference standard in patients with intermediate/high risk of prostate cancer. Material and Methods: A systematic search of PubMed, Embase, and the Cochrane Library was completed up to May 2020. We included studies investigating accuracy of 68Ga-PSMA PET/CT in primary lymph node staging before radical prostatectomy and PLND. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC) curve with an area under the curve (AUC) were synthesized. Results: Eleven studies comprising 904 patients were identified. Based on per-patient analysis, the pooled sensitivity and specificity reached 0.63 (95% CI: 0.46-0.78) and 0.93 (95% CI: 0.88-0.96), respectively, with the DOR of 22 (95% CI: 10-47). An overall accuracy was revealed by the SROC curve with AUC of 0.91 (95% CI: 0.88-0.93). Using the lymph node as unit, the pooled sensitivity and specificity were 0.70 (95% CI: 0.49-0.85) and 0.99 (95% CI: 0.96-1.00), respectively. And the DOR reached 167 (95% CI: 40-695) with an AUC of 0.96 (95% CI: 0.94-0.98). The pooled PPV and NPV all reached above 0.8 on basis of per-patient or per-node analysis. Conclusions: 68Ga-PSMA PET/CT represented as a promising test for preoperative lymph node staging and patients without lymph node metastatic status can rarely be misdiagnosed. However, its sensitivity ought to be improved before forgoing PLND.

Comparative efficacy of intravitreal pharmacotherapy for macular edema secondary to retinal vein occlusion: A protocol for the systematic review and network meta-analysis.

BACKGROUND: Multiple intravitreal pharmacotherapies including different anti-vascular endothelial growth factors (VEGF), intravitreal steroids, and combined therapy with anti-VEGF and steroids are available for patients with macular edema secondary to retinal vein occlusion (RVO). However, the recommendation of multiple therapies remains unknown. This study aims to evaluate the efficacy and safety of multiple intravitreal pharmacotherapies in patients with macular edema secondary to RVO. METHODS: We will systematically search the PubMed, Embase, and the Cochrane library for eligible studies. Randomized controlled trials (RCTs) with intravitreal pharmacotherapies for patients with macular edema secondary to RVO will be included. The Cochrane Collaboration's tool will be used to assess the risk of bias in the randomized trial. The primary outcome is the mean change in BCVA from baseline. The secondary outcomes are the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness from baseline and the number of serious adverse events. RESULTS: The result will obtain a comprehensive treatment recommendation for macular edema secondary to RVO. CONCLUSION: The results of the network meta-analysis will be submitted in a peer-reviewed journal for publication. ETHICAL STATEMENT: This article does not contain any studies with human or animal subjects performed by any of the authors.

Diagnostic Role of Magnetic Resonance Imaging-Targeted Biopsy for Prostate Cancer in Biopsy-Naïve Men: A Meta-Analysis.

OBJECTIVE: To investigate the diagnostic role of magnetic resonance imaging (MRI)-targeted biopsy (TB) for prostate cancer (PCa) in biopsy-naïve men. MATERIALS AND METHODS: Own control studies and randomized controlled trials (RCTs) up to December 2018 were identified via a systematic search of PubMed, Embase, Ovid, and the Cochrane Library. We pooled relative sensitivity (or risk ratio [RR]) to compare diagnostic efficiency for PCa and clinically significant PCa (csPCa) between TB and systematic biopsy (SB). The independent role of either biopsy pathway was evaluated for participants with positive/negative MRI. RESULTS: Thirty-one studies consisting of 25 own control studies and 6 RCTs were included. We identified 4,020 biopsy-naïve men with positive MRI who underwent two biopsies concurrently, with PCa/csPCa detection rates of 65.90 and 45.13%, respectively. TB and SB did not differ in the detection of any PCa (RR 0.98, 95% confidence interval [CI] 0.92-1.05). However, TB detected more csPCa (RR 1.19, 95% CI 1.10-1.30) and more PCa with a Gleason score ≥3+4 (RR 1.20, 95% CI 1.07-1.34). Using a combined test as a reference, omitting SB resulted in detecting 12.81% less csPCa and 20.76% less clinically insignificant PCa (cinsPCa), and omitting TB resulted in detecting 25.69% less csPCa and 10.8% more cinsPCa. For patients with negative MRI, omitting SB led to underdetection of 30.29% of any PCa (10.9% of csPCa). CONCLUSIONS: Combining TB and SB increased the diagnostic accuracy of csPCa for biopsy-naïve men with positive MRI, and omitting SB for patients with a negative MRI would lead to the underdetection of nearly 10% of csPCa.

Predictive value of preoperative neutrophil-to-lymphocyte ratio in non-metastatic papillary renal cell carcinoma patients after receiving curative surgery.

OBJECTIVE: To determine the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) for disease-free survival (DFS) in non-metastatic papillary renal cell carcinoma (pRCC) patients following partial or radical nephrectomy. METHODS: We retrospectively analyzed 315 non-clear cell RCC patients who received curative surgery in our hospital from 2013 to 2018, from which 76 pRCC patients without metastasis (T1-3N0M0) were selected. The receiver operating characteristics (ROC) curve was drawn and an NLR cut-off of 2.5 was set to achieve maximum diagnostic accuracy for predicting DFS. Kaplan-Meier method and the Cox regression model was used to determine the relationship of NLR with DFS. RESULTS: During a median follow-up of 28.0 months (IQR 15.9-42.1, mean 31.4), disease recurred in 12 patients (15.8%) recording a median duration of 14.4 months (IQR 8.6-22.9, mean 16.6). The 5-year DFS was 85.5% and 61.6% for the low (<2.5) and high (≥2.5) NLR groups respectively. According to Kaplan-Meier analysis, DFS was significantly lower in the high NLR group compared with that in the low NLR group (p=0.03). Univariate analysis revealed that high NLR level (HR 3.3, p=0.041), advanced pathological T stage (HR 10.1, p<0.001), larger tumor size (HR 1.2, p=0.008) and radical nephrectomy (HR 5.7, p=0.025) were associated with poor DFS, while multivariate analysis indicated that only advanced pathological T stage (HR 6.9, p=0.010) and high NLR level (HR 3.8, p=0.028) remained as the independent prognostic factors for poor DFS. CONCLUSION: A high preoperative NLR level was an independent prognostic marker for DFS in the patients of non-metastatic pRCC (pT1-3N0M0) following curative surgery. This can be used as an adjuvant tool to select patients for clinical trials or more frequent follow-up strategies.

Transperineal Magnetic Resonance Imaging-Targeted Biopsy May Perform Better Than Transrectal Route in the Detection of Clinically Significant Prostate Cancer: Systematic Review and Meta-analysis.

The diagnostic accuracy of magnetic resonance imaging (MRI)-targeted biopsy by using the transperineal (TP) versus transrectal (TR) route in the detection of clinically significant prostate cancer (csPCa) remains to be revealed. A systematic search of PubMed, Embase, Ovid, and the Cochrane Library up to April 2019 was conducted. We pooled odds ratios with 95% confidence intervals (CIs) for csPCa detected by TP and TR MRI-targeted biopsy. The relative sensitivity (or risk ratio) between TP and TR route was synthesized. We also pooled the diagnostic sensitivity of either approach using the combined biopsy results as the reference standard. A total of 328 patients with positive multiparametric MRI underwent TP MRI-targeted biopsy, and 315 patients underwent TR MRI-targeted biopsy. The TP route detected more csPCa, with a detection rate of 62.2% (204/328) compared to 41.3% (130/315) for the TR route (odds ratio = 2.37; 95% CI, 1.71-3.26). After adjusting for differences in cancer prevalence, TP MRI-targeted biopsy detected 91.3% (105/115) of csPCa compared to 72.2% (83/115) by the TR route (risk ratio = 1.26; 95% CI, 1.02-1.54). The pooled diagnostic sensitivity of the TP route (86%; 95% CI, 77-96) was better than the TR route (73%, 62-88%). The TR approach missed more csPCa located at the anterior zone of the prostate (20 vs. 3). The TP route performed better than the TR route in MRI-targeted biopsy, especially in detecting csPCa located at the anterior prostate. More large prospective randomized or head-to-head comparison studies comparing the two approaches are warranted.

Large Cell Neuroendocrine Carcinoma of the Prostate: A Systematic Review and Pooled Analysis.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the prostate is an extremely rare entity, and the clinicopathological course, potential effective treatment, and prognosis are yet to be elucidated. MATERIALS AND METHODS: A systematic search in Pubmed, Embase, and Ovid from inception to January 2019 was conducted. We reviewed each individual case of prostatic LCNEC and summarized specific features and outcomes for this rare pathologic entity. RESULTS: Thirteen studies with a total of 20 patients (mean age: 70.3, range 43-87) were included in our review. Seventeen patients harbored primary LCNEC of the prostate, of which 9 patients were diagnosed with de novo carcinoma, and 8 patients were with a history of prostatic adenocarcinoma treated with hormonal therapy (mean duration: 2.9 years, range 2-5). The other 3 patients were diagnosed with metastatic LCNEC originating from lung (2 cases) and bladder (1 case). All patients met the diagnostic criteria of the typical morphological features as well as immunohistochemical staining results. Nearly all primary de novo LCNEC of the prostate were at a late stage at initial diagnosis. The pattern of distant metastasis resembled that of prostatic adenocarcinoma with the most common sites as bone spread (8/16, 50%). Most patients received systematic chemotherapy after diagnosis; however, the prognosis remained poor and patients deteriorated rapidly but with exception. Three reported cases in the context of de novo LCNEC admixed with prostatic adenocarcinoma kept sustained response to androgen deprivation therapy (ADT) and achieved obviously better survival outcomes compared with other patients. CONCLUSIONS: LCNEC of the prostate is a rare entity that mostly occurs after long-standing hormonal therapy of prostatic adenocarcinoma. The prognosis was universally poor irrespective of the systematic chemotherapy. However, patients of de novo tumor mixed with prostatic adenocarcinoma may respond to ADT and harbor a better outcome than those of pure de novo or post-ADT LCNEC of the prostate.

Combined therapy and antivascular endothelial growth factor monotherapies for polypoidal choroidal vasculopathy: A protocol for the systematic review and network meta-analysis of efficacy and safety.

BACKGROUND: Different antivascular endothelial growth factor (VEGF) monotherapy regimens and photodynamic therapy (PDT) combined with anti-VEGF therapy are available for patients with polypoidal choroidal vasculopathy (PCV). However, the comparative efficacy and safety of different anti-VEGF monotherapy regimens and combined therapy with PDT and anti-VEGF remains unknown. The aim of our study is to evaluate the efficacy and safety of anti-VEGF monotherapies and combined therapy in patients with PCV. METHODS: We will systematically search PubMed, Embase, and the Cochrane library for eligible studies. The Cochrane Collaboration's tool for assessing the risk of bias in a randomized trial and the ROBINS-I tool will be used to assess the risk of bias in the included studies. The primary outcome is the mean change in best corrected visual acuity from baseline. The secondary outcomes are the mean change in central retinal thickness from baseline and the number of serious adverse events. RESULTS: The result will generate a comprehensive suggestion for the treatment of PCV. CONCLUSION: The results of the network meta-analysis will be submitted in a peer-reviewed journal for publication. ETHICS AND DISSEMINATION: The study does not involve human subjects and requires no ethical approval or patient consent. The results of the network meta-analysis will be submitted in a peer-reviewed journal for publication and generate a comprehensive suggestion for the treatment of PCV.

The role of fluorescence in situ hybridization to predict patient response to intravesical Bacillus Calmette-Guérin therapy for bladder cancer: A diagnostic meta-analysis and systematic review.

BACKGROUND: The aim of the study was to systematically review the relevant studies to assess the role of fluorescence in situ hybridization (FISH) test for predicting patient response to Bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT). METHODS: We searched PubMed, Embase, and the Cochrane Library from inception to July 5, 2018, and used Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We pooled sensitivity, specificity, and area under curve (AUC) of baseline and post-BCG FISH test for predicting tumor recurrence. Hazard ratio (HR) with 95% confidence intervals (95% CIs) and a Fagan nomogram were applied to assess predictive accuracy of post-BCG FISH test. RESULTS: A total of 6 studies with 442 participants for post-BCG test and 404 participants for baseline BCG test were included. The pooled analysis for post-BCG FISH test revealed the sensitivity of 0.54 (95% CI 0.38-0.69), specificity of 0.84 (95% CI: 0.72-0.91), and area under the curve (AUC) of 0.78 (95% CI: 0.74-0.81) for predicting tumor recurrence. Patients with positive post-BCG FISH test were more likely to recur during follow-up (HR 3.95, 95% CI 2.72-5.72). The Fagan nomogram revealed the "post-test" probability of tumor recurrence increased by 29% for patients with positive post-BCG FISH test. The baseline FISH test had a pooled sensitivity of 0.70 (95% CI 0.55-0.81), specificity of 0.41 (95% CI: 0.26-0.58), and AUC of 0.60 (95% CI: 0.56-0.64) for predicting recurrence. CONCLUSION: The post-BCG FISH test can predict BCG failure with high specificity and patients with positive post-BCG FISH test were more likely to recur. However, the relatively low sensitivity of post-BCG FISH test and unsatisfactory performance of baseline FISH test may limit their mono-use.

The role of real-time elastography-targeted biopsy in the detection and diagnosis of prostate cancer: A systematic review and meta-analysis.

BACKGROUND: The role of real-time elastography (RTE)-targeted biopsy in the detection and diagnosis of prostate cancer (PCa) remains controversial. METHODS: We searched Medline, Embase, and Cochrane Library from inception to July 31, 2017 and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess the quality of the identified studies. We applied the relative sensitivity value to assess the diagnostic accuracy of RTE-targeted biopsy using the 10-core systematic biopsy as the reference standard. RESULTS: Seven studies comprising 5 cohorts and 2 randomized controlled trials (RCTs) were included. Of the 5 cohorts that encompassed 698 participants, we found that RTE-targeted biopsy did not outperform systematic biopsy in either overall PCa detection (69.5% vs 80.5%, relative sensitivity 0.92, 95% CI 0.80-1.06) or for the initial biopsy (56.8% vs 64.0%, relative sensitivity 0.93, 95% CI 0.79-1.11). For the core-by-core analysis, more positive cores were detected by RTE-targeted biopsy than systematic biopsy (21% vs 11%, relative sensitivity 2.17, 95% CI 1.61-2.95). The 2 RCTs showed a favorable trend toward greater PCa detection when a combination of systematic biopsies and RTE-targeted biopsies was used than when systematic biopsy alone was used (45.5% vs 39.5%, risk ratio (RR) 1.18, 95% CI 0.98-1.43). CONCLUSION: Currently, there is not enough evidence to demonstrate that RTE-targeted biopsy can outperform systematic biopsy, but the combination of systematic and RTE-targeted biopsy may be a promising approach for improving PCa detection.