Reza Mirshahi

Background To evaluated changes in enucleation and globe preservation rates before and after the application of targeted chemotherapy approaches in unilateral and bilateral retinoblastoma (RB). Methods In this retrospective cohort study, 491 patients with 719 affected eyes were classified into T1 (2001–2012, inclusive) and T2 (2013–2024) based on the time of enucleation. The primary outcome was any enucleation. Secondary analyses evaluated international classification of retinoblastoma (ICRB)-specific outcomes, final anatomical preservation of the globe, time to enucleation, treatment patterns, and overall survival. Results The cohort included 263 patients with unilateral disease (263 eyes) and 228 patients with bilateral disease (456 eyes). In unilateral disease, enucleation decreased from 79 of 97 eyes (81.4%) in T1 to 99 of 166 (59.6%) in T2. In bilateral disease, enucleation decreased from 63 of 144 eyes (43.8%) to 83 of 312 (26.6%). T2 was associated with a 29% lower enucleation risk in unilateral disease (RR, 0.71; 95% CI, 0.63–0.80; P < 0.001) and a 45% lower risk in bilateral disease (RR, 0.55; 95% CI, 0.46–0.66; P < 0.001). The relative T1-to-T2 reduction was greater in bilateral RB (ratio of RRs, 0.78; 95% CI, 0.62–0.97; P = 0.026). The largest stage-specific improvement occurred in ICRB group D, with enucleation decreasing from 82.6% to 12.5% in unilateral RB and from 56.7% to 14.0% in bilateral RB. Eleven deaths occurred, limiting the precision of overall-survival comparisons. Conclusions The post-2012 treatment era was associated with substantially greater globe preservation rate in both unilateral and bilateral retinoblastoma, with particularly pronounced improvement in ICRB group D disease. Clinical trial registration Not applicable.

A subset of evidence indicate that the imaging parameters of macular OCTA correlate with the severity of DR. As the disease progress, higher grade of capillary density comprise occurs in retinal capillary layers. This is also observed in the peripapillary retinal nerve fiber layer (pRNFL), where the average pRNFL thickness and vascular density is reduced in diabetic patients, especially in eyes with non-proliferative DR (NPDR), compared to age-matched healthy objects. pRNFL capillary density had relatively high distinguishing ability to detect DR from healthy eyes.(5) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1404157/full) Recent studies investigating the progression of DR, has highlighted the vital predicting role of peripheral non perfusion in future complications. Ultrawide-field fluorescein angiography is the diagnostic tool that provides valuable insights to the degree of retinal ischemia. However, it is invasive with limited access in routine ophthalmology clinics. Guo et al. showed that ultrawidefield OCTA reveal the non-perfusion areas within its field of view, underscoring its potential role as a surrogate for an invasive diagnostic procedure.(6) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1485311/full) More extensive capillary nonperfusion in both superficial and deep retinal capillary layers has been suggested in eyes with DME. The current finding of reduced capillary vascular density, and altered choriocapillaris flow area accentuates the importance of retinal ischemia in the development of DME. (7) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1275200/full) The future longitudinal investigation, utilizing the OCTA parameters, can help predict eyes at risk for DME, and providing guide to devise prophylactic plans.The status of retinal vascular density could expand our understanding with some disease processes. Corneal microdots are highly reflective spherical structures found throughout the entire depth of cornea. OCTA could shed light on the mechanisms of microdots development. Low grade inflammation and relative ischemia could be the initiating factors, as these microdots appear more in corneas with diabetic retinopathy, and their prevalence had correlation with OCTA parameters.( 8) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1481018/full)The advent of artificial intelligence heralds future advancements in the care of patients with DR. Herein, we included a meta-analysis reporting the accuracy deep learning models on OCT and retinal imaging in the diagnosis of DR.( 6) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1485311/full) These models showed promising performance; however significant challenges are still remained to be addressed. Generating standardized datasets of imaging are a crucial infrastructural issue. Attention to include high quality OCTA images, with accepted image processing techniques, and developing a platform to uniformly compare data from various devices are of paramount importance that ensures high quality feed for deep learnings model. Subtle ocular characteristics should be considered in accurate reporting of OCTA images, including axial length, refractive error, or even mydrias.(9) (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1292255/full) Although presence of mydrias did not affect vascular density measurement in images with comparable quality score, this simple intervention can significantly affect the overall image quality in retinal clinic.The current topic, that explores diverse aspects of OCTA application in DR, adds an insight into the vast applicability of this imaging. Future investigations will complement the promising utility of OCTA as a non-invasive and accessible imaging modality in DR patients.

Background: Retinal capillary hemangioblastoma (RCH) is a benign tumor that frequently appears as the first manifestation in patients with von Hippel-Lindau (VHL) disease, potentially resulting in significant vision loss. Thus, recognizing and managing it promptly is crucial. Summary: New imaging techniques, including widefield optical coherence tomography (OCT) and OCT angiography, improve diagnostic accuracy and monitoring, facilitating early treatment and better prediction of visual outcomes. While traditional therapies such as laser photocoagulation, cryotherapy, and vascular endothelial growth factor inhibitors serve as the cornerstones of RCH therapy, new approaches, including tyrosine kinase inhibitors and hypoxia-inducible factor inhibitors, also exhibit promising results in treating resistant or recurrent tumors. Furthermore, genetic testing and counseling are beneficial for identifying patients linked to VHL disease, allowing early detection of systemic manifestations of this syndrome and enabling proper therapeutic management. Key Messages: This review consolidates the epidemiology, pathophysiology, clinical imaging, diagnostic evaluation, and treatment of RCH, emphasizing new insights pertinent to clinical practice and patient care.

Purpose: To investigate the association between high-risk histopathological features (HRHFs) and clinical indicators in advanced retinoblastoma and to identify independent predictors of high-risk disease. Methods: This single-center retrospective cohort study analyzed 236 enucleated eyes from patients with retinoblastoma treated at a tertiary referral center in Tehran, between 2001 and 2024. Clinical data and histopathological features were extracted. Eyes were classified into low-risk and high-risk groups based on HRHFs. Statistical analyses included univariate and multivariate logistic regression to identify factors independently associated with HRHFs. Results: Of the 236 eyes, 58 (24.6%) demonstrated HRHFs. Patients with high-risk tumors were significantly older at diagnosis (31.9 ± 19.2 vs. 22.3 ± 18.9 months, p = 0.017) and enucleation (37.3 ± 24.8 vs. 26.6 ± 23.3 months, p = 0.009). In multivariate analysis, four variables remained independently associated with HRHFs: increasing age at enucleation (OR = 1.015; 95% CI: 1.001–1.029; p = 0.038), higher tumor height (OR = 1.171; 95% CI: 1.073–1.279; p < 0.001), iris neovascularization (OR = 60.12; 95% CI: 6.93–521; p < 0.001), and both exophytic endophytic growth pattern (OR = 11.92; 95% CI: 2.04–70.28; p = 0.006). Rosette subtype, growth pattern, and tumor necrosis were not independently predictive after adjustment. Conclusions: Older age at enucleation, iris neovascularization, tumor height, and a combined exophytic endophytic tumor growth patterns are strong independent predictors of high-risk histopathologic features in retinoblastoma. Recognizing these indicators preoperatively may assist in risk stratification and guide treatment choices to enhance outcomes.

Introduction: This article presents the results of a prospective pilot study on circulating tumor DNA (ctDNA) monitoring in uveal melanoma (UM) patients, along with a systematic review of the literature to support and contextualize the findings. We investigated the clinical utility of ctDNA variant allele frequency (VAF) for early detection of tumor progression. Case Presentations: We performed serial ctDNA testing using the Ion AmpliSeq Cancer Hotspot Panel v2 and Ion Proton™ sequencing in 3 UM patients (two recurrent, one nonrecurrent) at four time points over 2 years. A systematic review of studies up to June 2024 was also conducted, identifying 32 additional UM patients. In recurrent patients, co-occurring mutations in GNAQ, GNAS, and IDH1 were identified at the time of recurrence, with minimum VAFs of 0.51%, 0.25%, and 0.1%, respectively. In the nonrecurrent patient, pathogenic variants were absent, and VAFs of key genes declined over time. The systematic review supported the association of ctDNA alterations with recurrence and metastasis, identifying critical genes including GNAQ/11, GNAS, IDH1, STK11, FGFR2, and EGFR, many of which interact with the BAP1 signaling pathway. Conclusion: Serial ctDNA analysis may serve as a noninvasive tool for early detection of recurrence in UM. Co-occurrence of GNAQ, GNAS, and IDH1 mutations may represent a molecular signature of recurrence. Further validation in larger cohorts is needed to define optimal gene panels and VAF thresholds for clinical use.

We compared chorioretinal microvascular of Slow Coronary Flow Phenomenon (SCFP) patients using Optical Coherence Tomography Angiography (OCTA) to healthy controls. We recruited 21 patients from September 2023 until January 2024 from two referral centers. We enrolled 21 age-sex-matched controls retrospectively. Patients were referred to obtain OCTA in our outpatient ophthalmology clinic. The OCTA and Enhanced Depth Imaging (EDI) OCT findings were measured. Whole image and perifoveal Vascular Density (VD) of superficial and deep capillary plexuses and Parafoveal VD of superficial layer were diminished in SCFP groups compared to controls (p < 0.05) while both superficial and deep foveal VD and deep parafoveal VD were spared. Sub-Foveal Choroidal Thickness (SFCT) was significantly thinned compared to controls (p < 0.05), while central macular thickness, choroidal vascularity index, and choriocapillaris flow were similar between groups. SFCT was the only independent predictor of SCFP on multivariable regression analysis. Parafoveal superficial VD and SFCT showed the strongest ability to distinguish between SCFP patients and healthy controls (AUC: 0.80, 0.79, respectively). Additionally, whole image and perifoveal VD in both superficial and deep capillary plexus demonstrated at least moderate discriminatory power. We found that decreased retinal microvascular density may serve as a potential biomarker for the diagnosis of SCFP. Additionally, SCFP patients had considerably thinner SFCTs than controls. Parafoveal superficial VD and SFCT showed the highest potential in distinguishing between individuals with SCFP and healthy individuals. SCFP is likely linked to anomalies in the small blood vessels of the retina and choroid. However, further studies are needed to confirm this association and to control for the potential confounding effects of diabetes and hypertension.

Purpose: To assess the colocalization of ellipsoid zone (EZ) disruption with nonperfusion in choriocapillaris (CC), retinal superficial capillary plexus (SCP), and deep capillary plexus (DCP) in diabetic patients using en face optical coherence tomography (OCT) and OCT angiography (OCTA).Methods: Macular OCT and OCTA scans (3 × 3 mm) of 41 patients with diabetic retinopathy were obtained using an RTVue XR Avanti instrument. After correcting the shadow artifacts, EZ integrity was assessed in the en face OCT slab using the Gaussian mixture model clustering method compared with the corresponding EZ en face OCT of 11 age‐matched normal patients. A similar technique was used for detecting capillary nonperfusion using CC en face OCTA. Geometric perfusion density (GPD) maps were also generated for the SCP and DCP. Maps of capillary nonperfusion in the CC, SCP, and DCP were compared pixel by pixel with the map generated from EZ disruption.Results: Twenty‐one patients with diabetic macular edema (DME) and 20 patients with diabetic retinopathy without macular edema were included in this study. In both groups, the overlap of EZ disruption was significantly greater with choriocapillaris nonperfusion than with nonperfusion in the SCP and DCP (dry macular group: 33.15% with CC vs. 0.46% with SCP vs. 1.70% with DCP, p < 0.001; DME group: 29.81% with CC vs. 1.22% with SCP vs. 6.25% with DCP, p < 0.001). In multivariate analysis, after adjusting for stage of diabetic retinopathy and DME, EZ disruption was only associated with nonperfusion in CC (p value = 0.03). According to the linear regression model, there was a statistically significant correlation between logMAR visual acuity and EZ disruption in the dry macular group (p = 0.041).Conclusion: In patients with diabetic retinopathy, choriocapillaris nonperfusion may play a more significant role in photoreceptor loss than retinal nonperfusion.

Purpose: To compare the occurrence and characteristics of retinal displacement following direct perfluorocarbon liquid (PFCL)-silicone oil (SO) exchange versus indirect PFCL for air and air for SO exchange methods during pars plana vitrectomy (PPV) in patients with rhegmatogenous retinal detachment (RRD). Methods: A comparative case series study was conducted on 58 eyes with recent RRD, undergoing standard three-port PPV with SO tamponade. Fluid exchange was performed using either direct or indirect methods. Postoperatively, a comprehensive ophthalmic examination and fundus autofluorescence (FAF) imaging were conducted at one month. The presence, amount, and direction of retinal displacement were assessed based on FAF imaging and compared between the direct and indirect fluid exchange groups. Results: FAF imaging at one month revealed retinal displacement in 41.4% of eyes in the direct group and 62.1% in the indirect group, with no statistical difference between them ( P  = 0.537). However, the mean displacement was significantly higher in the indirect group (282.61 ± 110.83 µm) compared to the direct group (220.33 ± 39.67 µm, P  = 0.04). The direction of displacement (downward or upward) did not differ significantly between the groups ( P  = 0.093). Conclusions: While the occurrence and location of postoperative retinal displacement did not significantly differ between direct and indirect fluid exchange methods during PPV for RRD, eyes treated with the direct method exhibited lower mean displacement compared to the indirect method. These findings suggest potential benefits of the direct exchange approach in minimizing retinal displacement following surgery.