Efficacy of topotecan nanoparticles for intravitreal chemotherapy of retinoblastoma.

Retinoblastoma (Rb) is the most common intraocular malignancy in children that accounts for approximately 4% of all pediatric malignancies. Since chemotherapy is a widely practiced treatment for Rb, there is a growing interest in developing new and effective drugs to overcome systemic and local side effects of chemotherapy to improve the quality of life and increase the chances of survival. This study sought to fabricate thiolated chitosan nanoparticles containing topotecan (TPH-TCs-NPs) with a view of enhancing drug loading and release control. This research was also designed to assess the ability of TPH-TCs-NPs to improve cell association, increase treatment efficacy in retinoblastoma cells and xenograft-rat-model of retinoblastoma, and overcome current topotecan hydrochloride (TPH) intravitreal administration challenges, including stability loss and poor cellular uptake. Modified ionic gelation method was optimized to fabricate TPH-TCs-NPs and TPH-TMC-NPs (N-trimethyl chitosan nanoparticles containing TPH). We characterized the NPs and quantified topotecan loading and release against a free TPH standard. The efficacy of TPH-NPs was quantified in human retinoblastoma cells (Y79) by XTT and flow cytometry measurement. In addition, Y79 cells were injected intravitreally in both eyes of immunodeficient wistar albino rats to create a xenograft-rat-model to compare the antitumor effectiveness of TPH-NPs and TPH by intravitreal administration. TPH-NPs complexation was confirmed by EDX, FTIR, and DSC techniques. TPH-TCs-NPs and TPH-TMC-NPs had high encapsulation efficiency (85.23 ± 2 and 73.34 ± 2% respectively). TPH-TCs-NPs showed a mean diameter, polidispersity index, and zeta potential of 25±2 nm, 0.21 ± 0.03 and +12 ± 2 mV, respectively. As a function of dose, TCs and TMC NPs were more efficacious than free topotecan (IC50s 53.17 and 85.88 nM, relative to 138.30 nM respectively, P = 0.012). Kruskal-Wallis test showed a statistically significant difference between the groups. Additionally, a significant difference between the tumor control and TPH-TCs-NPs treated group in xenograft-rat-model ( Range of P-value: 0.026 to 0.035) was shown by Bonferroni post hoc test. The current investigation demonstrated enhanced efficacy and association of TPH-TCs-NPs relative to free TPH in retinoblastoma cells and tumor in vitro and in vivo.

Long term features of diabetic retinopathy in streptozotocin-induced diabetic Wistar rats.

Diabetic retinopathy is a complication of diabetes and a leading cause of vision loss among working-age adults. To assess whether the Wistar rat with Streptozotocin (STZ)-induced diabetes is a suitable animal model of human proliferative diabetic retinopathy we evaluated the vascular changes to assess the diabetic retinopathy (DR) stages in this model. After two weeks of intraperitoneal STZ (55 mg/kg) injection in male Wistar rats (270-300 g), they were considered diabetic with persistent blood glucose levels ≥ 16.65 mmol/L. The diabetic and control rats were investigated after 1, 3, 6 and 9 months by electroretinography, Evans blue assay, dextran fluorescence retinal angiography, and retinal histopathological studies. Retinal vascular permeability in the diabetic groups increased significantly in all diabetic groups. The amplitude of a- and b-waves decreased significantly in all diabetic groups compared with the age-matched control groups. The latent time of a-waves in the diabetic groups was delayed at 3 months of diabetes and this delay remained relatively constant till 9 months following the onset of diabetes. Although the latent time of b-wave in the diabetic groups increased slightly, a significant difference was found right at 9 months of diabetes. Vascular density and branching point numbers significantly decreased in the diabetic eyes at 3 and 6 months while they increased at 9 months, which was not significant. Intraretinal hemorrhage and ischemic changes were detected in the half of diabetic rats after 6 months and considered as preproliferative stage of diabetic retinopathy. Although preproliferative changes were detected in all diabetic rats at 9 months, half of them showed vitreous neovascularization attached to retina and retinal folds which can be considered as proliferative stage of DR. Intraretinal hemorrhage, extensive leakage of fluorescein, retinal folds, and vitreous neovascularization were the most prominent findings of severe and proliferative diabetic retinopathy in a fraction of the STZ-induced diabetic rats which were comparable to that of the human patients. STZ-induced diabetic rats can be considered to be a potentially useful model for studies on pathogenesis and treatment of diabetic retinopathy in human.

The rate of endophthalmitis after pars plana vitrectomy and its risk factors.

PURPOSE: To study the incidence of endophthalmitis after pars plana vitrectomy, its causative organisms, and visual acuity outcomes. PATIENTS AND METHODS: In this retrospective, comparative study, the medical records of patients with acute-onset postoperative endophthalmitis after pars plana vitrectomy at Farabi Eye Hospital, Tehran, Iran, during a 12-year period between January 2004 and November 2015 were reviewed. To compare the endophthalmitis patients with other cases who underwent pars plana vitrectomy at the same day and also the same operating room, a control group was developed by gathering the data from surgical records. RESULTS: In the present study, the incidence rate of pos- vitrectomy endophthalmitis was 0.04% (16/39783). The organisms identified in aqueous or vitreous cultures (culture positive 44%) included Streptococcus pneumoniae (two patients, 12.5%), Pseudomonas aeruginosa (two patients, 12.5%), fungi (two patients, 12.5%), and Streptococcus viridans (one patient, 6.25%). Visual acuity after treatment for endophthalmitis ranged from light perception (7 eyes) to hand motion (1 eye), and evisceration was performed in 8 eyes (50%). When comparing the cases (patients developing endophthalmitis) and controls (patients with no complications operated in the same day and place of operation with the case group), only not using tamponade showed a statistically significant relation with the occurrence of endophthalmitis (p = 0.034). CONCLUSION: Our results indicated low incidence of endophthalmitis after pars plana vitrectomy comparable to previous studies which resulted in poor visual acuity. It seems that not using tamponade might increase the risk of endophthalmitis among these patients.

Dental pulp stem cells differentiation into retinal ganglion-like cells in a three dimensional network.

The loss of retinal ganglion cells (RGCs) in majority of retinal degenerative diseases is the first seen pathological event. A lot of studies aim to discover suitable cell sources to replace lost and damaged RGCs. Among them dental pulp stem cells (DPSCs) have a great potential of differentiating into neuronal lineages as well as RGCs. Moreover, three-dimensional (3D) networks and its distribution for growing and differentiation of stem cells as much as possible mimic to native tissue holds great potential in retinal tissue engineering. In this study, we isolate DPSCs from rat incisors and validate them with flow cytometry. Briefly, we differentiated cells using DMEM/F12 containing FGF2, Shh and 0.5% FBS into retinal ganglion-like cells (RGLCs) in two conditions; 3D state in biocompatible fibrin hydrogel and two-dimensional (2D) or conventional culture in polystyrene plates. Immuncytochemical and gene expression analysis revealed the expression of Pax6, Atoh7 and BRN3B increased in 3D fibrin culture compared to 2D conventional culture. In combination, these data demonstrate that using 3D networks can resemble near natural tissue properties for effective generating RGCs which used to treat neurodegenerative diseases such as glaucoma.

Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

OBJECTIVE: To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). MATERIALS AND METHODS: 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4 mg plus sildenafil 50mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient's ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. RESULTS: Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). CONCLUSION: It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

Distribution and prevalence of refractive error in Iranian adult population results of the PERSIAN eye cohort study PECS.

The Persian Eye Cohort Study, a population-based cross-sectional study from 2015 to 2020, examined refractive error prevalence among 48,618 Iranian adults aged 31 to 70. The study encompassed six centers in Iran, employing random cluster sampling for demographic, medical, and socioeconomic data collection through interviews. Ophthalmic exams included visual acuity, automated and manual objective refraction, subjective refraction, slit lamp, and fundus examinations. Using the spherical equivalent definition, the sample population was categorized into groups. Results indicated a mean age of 49.52 ± 9.31 and a mean refractive error of 0.26 diopters (D) ± 1.6 SD (95% CI - 0.27 to -0.24), ranging from -26.1 to + 18.5 SD. Prevalence of myopia (< -0.5D) and hyperopia (> + 0.5D) was 22.6% (95% CI 22.2-23%) and 12.5% (95% CI 12.1-12.8%), respectively. Regarding different age groups, the prevalence of hyperopia and astigmatism exhibited a steady and significant rise with increasing age (p-value < 0.001 for both). The prevalence of Myopia, however, showed a distinctive pattern, initially increasing in adults under 45, declining in those aged 55-64, and rising again among individuals aged 60 and older. Female gender, older age, urban residency, higher education, higher income, and Fars ethnicity were significantly related to a higher prevalence of myopia (p-value < 0.001 for all). Female gender (p-value < 0.001), aging (p-value < 0.001), urban residency (p-value = 0.029), and lower-income (p-value = 0.005) were significantly related to higher prevalence of hyperopia. Astigmatism (> 1D) was prevalent in 25.5% of participants (95% CI 25.1-25.9%) and correlated with male gender, aging, urban residency, illiteracy, and higher income (p-value < 0.001, < 0.001, < 0.001, < 0.001, 0.014, respectively). The study's comparison with regional and international surveys highlighted the increase in myopia among those over 65 due to higher nuclear cataract rates in older adults. Myopia positively related to education, income, and urban residency, while hyperopia did not exhibit such associations.

Pain score of patients undergoing single spot, short pulse laser versus conventional laser for diabetic retinopathy.

BACKGROUND: To compare pain score of single spot short duration time (20 milliseconds) panretinal photocoagulation (PRP) with conventional (100 milliseconds) PRP in diabetic retinopathy. METHODS: Sixty-six eyes from 33 patients with symmetrical severe non-proliferative diabetic retinopathy (non-PDR) or proliferative diabetic retinopathy (PDR) were enrolled in this prospective randomized controlled trial. One eye of each patient was randomized to undergo conventional and the other eye to undergo short time PRP. Spot size of 200 µm was used in both laser types, and energy was adjusted to achieve moderate burn on the retina. Patients were asked to mark the level of pain felt during the PRP session for each eye on the visual analog scale (VAS) and were examined at 1 week, and at 1, 2, 4 and 6 months. RESULTS: Sixteen women and 17 men with mean age 58.9 ± 7.8 years were evaluated. The conventional method required a mean power of 273 ± 107 mW, whereas the short duration method needed 721 ± 406 mW (P = 0.001). An average of 1,218 ± 441 spots were delivered with the conventional method and an average of 2,125 ± 503 spots were required with the short duration method (P = 0.001). Average pain score was 7.5 ± 1.14 in conventional group and 1.75 ± 0.87 in the short duration group (P = 0.001). At 1 week, 1 month, and 4 months following PRP, the mean changes of central macular thickness (CMT) from baseline in the conventional group remained 29.2 µm (P = 0.008), 40.0 µm (P = 0.001), and 40.2 µm (P = 0.007) greater than the changes in CMT for short time group. CONCLUSION: Patient acceptance of short time single spot PRP was high, and well-tolerated in a single session by all patients. Moreover, this method is significantly less painful than but just as effective as conventional laser during 6 months of follow-up. The CMT change was more following conventional laser than short time laser.

Percutaneous nephrolithotomy in high-risk patients: a single-center experience with more than 350 cases.

PURPOSE: To assess the surgical outcomes and peri- and postoperative complications following percutaneous nephrolithotomy (PCNL) in high- and low-risk patients according to the American Society of Anesthesiologists (ASA) score. MATERIALS AND METHODS: We reviewed the patient records of 2,281 cases older than 18 years who had undergone PCNL in the 3 previous years. The patients were divided into two groups: a low-risk group (ASA score 1, 2: 1,922 cases) and a high-risk group (ASA score 3, 4: 359 cases). RESULTS: Analysis of the location and size of the stone, number and type of access, surgical approach, post-PCNL serum hemoglobin and decrease in glomerular filtration rate revealed no significant difference between the two groups. The stone-free rate was similar in both groups and the hospital stay in the high-risk patients was significantly greater than in the low-risk cases. 95% of low-risk and 91% of high-risk cases had surgical complications compatible with grade ≤II (Clavien system) and overall distribution of different grades of surgical complications was similar between the two groups (p = 0.177). CONCLUSION: Success rate and surgical complications of PCNL in high-risk patients were comparable to low-risk patients. It seems that PCNL may be a safe and effective procedure even in high-risk patients.

Achieving a one-year-tumor-free survival in a female with primary large cell neuroendocrine carcinoma of the urinary bladder and liver metastasis; a case report.

Primary neuroendocrine tumor (NET) of bladder is rare. It has four subtypes, and large cell neuroendocrine carcinoma (LCNEC) is the rarest. LCNEC affects mostly men over 60. Most common symptom is gross hematuria. It has no specific treatment. Metastasis is common and once occurred, average survival would be less than three months. Herein we present diagnostic and therapeutic management of a 65-year-old female with LCNEC of bladder and concurrent high-grade urothelial carcinoma. Despite developing early liver metastasis, she achieved a one-year tumor-free survival.

Retinal Tissue Engineering: Regenerative and Drug Delivery Approaches.

In recent decades, the improvement of photoreceptor-cell transplantation has been used as an effective therapeutic approach to treat retinal degenerative diseases. In this review, the effect of different factors on the differentiation process and stem cells toward photoreceptors along with cell viability, morphology, migration, adhesion, proliferation, and differentiation efficiency is discussed. Scientists are researching to better recognize the reasons for retinal degeneration, as well as discovering novel therapeutic methods to restore lost vision. In this field, several procedures and treatments in the implantation of stem cells-derived retinal cells have been explored for clinical trials. However, the number of these clinical trials is too small to draw sound decisions about whether stem-cell therapies can offer a cure for retinal diseases. Nevertheless, future research directions have started for patients affected by retinal degeneration and promising findings have been obtained.

The Antitumor Effect of Topotecan Loaded Thiolated Chitosan-Dextran Nanoparticles for Intravitreal Chemotherapy: A Xenograft Retinoblastoma Model.

Purpose: This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model. Methods: The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration. Results: NPs had a mean diameter, polydispersity index, and zeta potential of 30 ± 4 nm, 0.24 ± 0.03 and +10 ± 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 ± 2%) and vitreous seeds (89 ± 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P > 0.05). Conclusion: This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model.

PERSIAN Eye Cohort Study (PECS): Design, Methodology.

BACKGROUND: To report the study protocol, methodology and latest enrollment data of a large epidemiological multi-central eye cohort named PERSIAN Eye Cohort Study (PECS), originating from the ongoing PERSIAN Cohort Study, to investigate the distribution of ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. METHODS: A central committee designed the study and equipped six chosen centers (Khameneh, Some'e Sara, Hoveizeh, Yazd, Rafsanjan and Zahedan). A focal point in each center conducted the study under close supervision of the central committee. RESULTS: This ongoing study was launched in 2014. Out of 65,580 eligible participants of the PERSIAN Cohort, 48,618 individuals aged 35-70 have been enrolled in the PECS (response rate: 74.13%) until June 2021. Slit lamp and fundus photography were performed for 28,702 (59.03%) and 27,437 (56.43%) individuals, respectively. CONCLUSION: This large epidemiological multi-central eye cohort can improve our epidemiological knowledge of the prevalent ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. This will be very useful for future planned nationwide and global interventions.

Posttraumatic endophthalmitis: report No. 2.

PURPOSE: To study predisposing factors of endophthalmitis in patients with open-globe injury. METHODS: All 2,340 patients with open-globe injury admitted to our center over 5 years were studied retrospectively, and patients with endophthalmitis were compared with other patients. RESULTS: The number of endophthalmitis cases among patients with open-globe injury was 117 eyes, accounting for an incidence of 5.1%. The risk of endophthalmitis was significantly higher among male patients with pure corneal injuries (6.8%), intraocular foreign bodies (9.3%), traumatic lens rupture (7.1%), trauma resulting from needles (22.2%), and shorter lacerations. The existence of hyphema or iris prolapse was associated with lower rates of endophthalmitis. The mean gap between injury time and operation time was longer in the endophthalmitis group (2.1 ± 1.8 vs. 1.1 ± 1.3 days). Patients with endophthalmitis had significantly lower ocular trauma scores compared with other patients. CONCLUSION: Posttraumatic endophthalmitis is more likely among patients with open-globe injury that are needle related and among those who have intraocular foreign bodies, traumatic lens rupture, smaller wounds, or wounds exclusively in the cornea. Lower ocular trauma scores in this group of patients with penetrating trauma indicated a greater risk of poor visual prognosis. Therefore, it is suggested that necessary measures and immediate treatment be undertaken in high-risk patients.

Erratum: Biodistribution of Cy5-labeled Thiolated and Methylated Chitosan-Carboxymethyl Dextran Nanoparticles in an Animal Model of Retinoblastoma.

[This corrects the article DOI: 10.18502/jovr.v17i1.10171.].

Biodistribution of Cy5-labeled Thiolated and Methylated Chitosan-Carboxymethyl Dextran Nanoparticles in an Animal Model of Retinoblastoma.

PURPOSE: The use of more potent medicine for local chemotherapy of retinoblastoma in order to minimize local and systemic adverse effects is essential. The main goal of this investigation was to assess the biodistribution of thiolated and methylated chitosan-carboxymethyl dextran nanoparticles (CMD-TCs-NPs and CMD-TMC-NPs) following intravitreal (IVT) injection into rat eyes with retinoblastoma. METHODS: An ionic gelation method was used to fabricate Cy5-labelled CMD-TCs-NPs and CMD-TMC-NPs. The NPs were characterized. Cellular internalization of Cy5-labelled NPs was investigated using confocal microscopy and the absorption of labeled NPs was quantified by flow cytometry in human retinoblastoma (Y79) cells. In addition, the Cy5-labeled distribution of nanoparticles in the posterior segment of the eye was histologically imaged by confocal microscopy after IVT injection of NPs into the eyes of rats with retinoblastoma. RESULTS: CMD-TCs-NPs and CMD-TMC-NPs showed a mean diameter of 34 ± 3.78 nm and 42 ± 4.23 nm and zeta potential of +11 ± 2.27 mV and +29 ± 4.31mV, respectively. The in vivo study of intraocular biodistribution of Cy5-labeled CMD-TCs-NPs and CMD-TMC-NPs revealed that there is more affinity of CMD-TCs-NPs to the retina and retinoblastoma tumor after IVT administration while methylated chitosan nanoparticles are immobilized in the vitreous and are not able to reach the retina even after 24 hr. CONCLUSION: The ionic gelation technique was efficient in synthesizing a biocompatible polymeric nanosystem for drug delivery into the posterior segment of the eye. The current study demonstrated increased ocular bioavailability of CMD-TCs-NPs relative to CMD-TMC-NPs in retinoblastoma induced rat eyes.

Prevalence and Burden of Refractive Errors at National and Sub-national Levels in Iran.

PURPOSE: To estimate the prevalence, burden of refractive errors and their associated trend from 1990 to 2018 and geographic inequalities in Iran. METHODS: Data regarding the epidemiology of refractive errors was extracted from three different sources: systematic review of published literature, data from visual school screening programs, and data from Iran's national health survey (NHS). The pool of all available data on refractive errors as well as demographic, location, and socioeconomic status covariates were fitted in spatio-temporal and Gaussian process regression models to predict the prevalence of refractive errors from the years 1990 to 2018 in 31 provinces grouped by age and sex in order to calculate years lived with disability (YLDs). RESULTS: In 2018, the age-adjusted prevalence of refractive errors was 16.32% (95% uncertainty interval [UI]: 12.44-21.48%) in both sexes, 17.98% (95% UI: 13.74-23.61%) in women, and 14.66% (95% UI: 11.14-19.36%) in men. The prevalence of refractive errors reveals that it increases with age. Refractive errors contributed to 441.41 and 348.38 YLDs in men and women, respectively. The age-standardized prevalence growth was 31.30% in females and 24.32% in males from the years 1990 to 2018. Significant geographical heterogeneity was observed. The age-standardized YLDs rates of refractive errors represent an increasing trend of 28.9% increase from 1990 to 2018. CONCLUSION: Over 28 years, the prevalence of refractive errors increased significantly. Women tend to have higher rates of prevalence. The prevalence increased in older ages. Border provinces had the lowest prevalence. Age-standardized YLDs rates of refractive errors increased by about 30%.

Risk Factors for Uncorrected Refractive Error: Persian Cohort Eye Study - Rafsanjan Center.

Purpose: To determine the prevalence of visually significant uncorrected refractive error (URE) in Rafsanjan and investigate the related factors. URE is the leading cause of visual impairment (VI) which causes the second-highest number of years lived with disability. The URE is a preventable health problem. Methods: In this cross-sectional study participants from Rafsanjan who were 35-70 years were enrolled between 2014 and 2020. Demographic and clinical characteristics data were gathered, and eye examination was performed. Visually significant URE was defined as present if habitual visual acuity was (HVA; visual acuity with present optical correction) >0.3 logMAR in the best eye and the visual acuity of that eye showed >0.2 logMAR improvement after the best correction. Logistic regression was used to determine the association between predicting variables (age, sex, wealth, education, employment, diabetes, cataract, and refractive error characteristics) and outcome (URE). Results: Among the 6991 participants of Rafsanjan subcohort of the Persian Eye Cohort, 311 (4.4%) had a visually significant URE. Diabetes was significantly more prevalent in the participants with visually significant URE, at 18.7% versus 13.1% in patients without significant URE (P = 0.004). In the final model, each year of increase in age was associated with 3% higher URE (95% confidence interval [CI]: 1.01-1.05). In comparison to low hyperopia, participants with low myopia had 5.17 times more odds of visually significant URE (95% CI: 3.38-7.93). However, antimetropia decreased the risk of visually significant URE (95% CI: 0.02-0.37). Conclusion: Policymakers should pay special attention to elderly patients with myopia to effectively reduce the prevalence of visually significant URE.

Flat irregular pigment epithelial detachment over time and outcome of different treatment regimens.

To present long-term visual and structural outcome of treatment in two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes within pachychoroid spectrum. Prospective interventional case series. FIPED were classified into two subgroups; aFIPED and vFIPED based on OCTA. aFIPED underwent PDT, and vFIPED underwent either PDT, IVB, or combination of PDT&IVB. Vision, subretinal or intraretinal fluid, and choroidal biomarkers such as choroidal thickness, area, choroidal vascular index (CVI), and PED area were measured at baseline and last follow-up. Fifteen eyes with aFIPED were followed for a mean of 14.7 ± 10.8 months. Their vision improved, (0.44 ± 0.37-0.33 ± 0.40 LogMAR, p = 0.009) with significant reduction of fluid, choroidal area, thickness, PED area and increase in CVI. Twenty eyes with vFIPED were followed for a mean of 16.5 ± 8.2 months. The same pattern of choroidal alterations without visual improvement was observed in eyes underwent PDT alone. Combination therapy resulted in improvement of vision (0.38 ± 0.10-0.23 ± 0.17 LogMAR, p = 0.006) with reduction of choroidal area and thickness, with an increase in CVI. IVB alone could not change vision or choroidal structure. Single session PDT may lead to sustained visual improvement and structural change in eyes with aFIPED. Combination of PDT and IVB may be a better choice in eyes with vFIPED.

Comparison of Single Monthly Instillations of Intra-Vesical Bacillus Calmette-Guerin Maintenance Therapy with Southwest Oncology Group Regimen in Non-Muscle Invasive Bladder Cancer Patients-A Retrospective Analysis In a Single Institute.

PURPOSE: To compare the efficacy and complication rate of monthly instillations of Bacillus Calmette-Guerin (BCG) as maintenance therapy in intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with the current standard Southwest Oncology Group (SWOG) protocol. MATERIALS AND METHODS: In this observational retrospective study, 40 intermediate and high risk NMIBC patients, receiving standard BCG maintenance regimen, were compared with another 40 NMIBC patients, undergoing monthly intra-vesical instillations of BCG with regard to recurrence, progression and major and minor adverse effects. RESULTS: The two groups were similar in their basic characteristics except for the older age in the monthly instillation group ( 70.95 ± 9.66 years vs. 64 ± 8.8, p = 0.001). Study objectives between the monthly instillation group and the standard group, including recurrence ( 17.5 % vs. 25%, p = 0.34) and progression rate ( 7.5% vs. 10%, p = 0.54) did not show statistically significant difference. Major and minor complication rate also did not show any difference between the two groups. CONCLUSION: In addition to the currently recommended standard protocol of BCG maintenance therapy, our study shows that the monthly regimen can be recommended in intermediate and high risk NMIBC patients without compromising the efficacy of the treatment.

Fibrinogen prophylaxis for reducing perioperative bleeding in patients undergoing radical cystectomy: A double-blind placebo-controlled randomized trial.

OBJECTIVE: Excessive bleeding is an important complication of radical cystectomy. We aimed to assess whether preoperative administration of fibrinogen decreases perioperative bleeding and improves the outcome of radical cystectomy. DESIGN: Double-blinded randomized trial with two parallel arms. SETTING: The study was conducted in the department of surgery at a teaching hospital affiliated with a University of Medical Sciences. PATIENTS: In total, 70 men undergoing radical cystectomy were randomized to fibrinogen (n = 35) and placebo-control groups. Mean (SD) age was 64.7 (7.4) years. INTERVENTIONS: The intervention group received 2 g fibrinogen concentrate diluted in 100 ml distilled water, and the control group received 100 ml normal saline; both intravenously 15 ̶ 30 min before the start of the surgery. OUTCOME MEASURES: The primary outcome was the amount of perioperative blood loss. The secondary outcomes were hemodynamic features and vital signs. MAIN RESULTS: Fibrinogen significantly decreased the volume of blood loss (p < 0.001) and the total number of transfused packed-cell units per group (38 vs. 115 units); and compensated the decrease of HCO3 (p = 0.030), the mean arterial pressure (p < 0.001), hemoglobin O2 saturation (p = 0.001), heart rate (p < 0.001), and temperature (p < 0.001) throughout the surgery compared with the placebo. Patients in the fibrinogen group had shorter Intensive Care Unit (p = 0.001) and hospital (p < 0.001) stay. We did not find any adverse reaction in our patients receiving fibrinogen concentrate. CONCLUSION: Fibrinogen concentrate reduces perioperative bleeding and the need for blood transfusion in radical cystectomy. It improves the outcomes of the surgery and decreases patients' length of stay in the healthcare system following radical cystectomy. REGISTRATION: Iranian Registry of Clinical Trials (IRCT) http://www.irct.ir/, reference number: IRCT20191013045091N1. ETHICS CODE: Shahid Beheshti University of Medical Sciences, reference number: IR.SBMU.RETECH.REC.1398.033.