PURPOSE: To describe an alternate surgical technique for fluocinolone acetonide (Retisert) implantation in patients with extensive pars plana and pars plicata fibrosis secondary to chronic non-infectious uveitis. METHODS: This retrospective, interventional case series included five eyes of four patients who had poorly controlled chronic non-infectious uveitis. Retisert was implanted successfully using a novel approach. The device was introduced into the posterior segment through the anterior chamber and posterior capsulotomy, forgoing the need for full-thickness scleral incision and minimizing the risk of retinal detachment and associated complications. RESULTS: Five eyes underwent passage of Retisert implant through the anterior segment via a limbal incision and a posterior capsulotomy. Retisert was successfully implanted in all patients in the posterior chamber. No intraoperative or postoperative complications were encountered. Up until the last follow-up, all eyes demonstrated the stability of the implant. Visual acuity improved in four out of five eyes. CONCLUSIONS: Retisert can be implanted via the anterior chamber in patients with extensive fibrosis in the pars plana and pars plicata regions. This approach may minimize the risk of retinal traction and damage to the implant when compared to the traditional full-thickness sclerotomy method in these high-risk cases.

PURPOSE: Epidemiologically, men have a higher incidence, severity, and progression of diabetic retinopathy (DR) than women. We investigated microvascular differences between men and women with diabetes on optical coherence tomography angiography (OCTA). METHODS: Three × 3 mm OCTA macula scans of non-diabetic and patients with diabetes were obtained. Vascular parameters included parafoveal vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) as well as foveal avascular zone (FAZ) area and perimeter. Multivariable linear regression was used for statistical analysis. RESULTS: There were 1809 patients with diabetes and 217 non-diabetic participants that were included in this study. Diabetic individuals included those with no DR (n = 1356), mild non-proliferative DR (NPDR; n = 286), moderate NPDR (n = 126), and severe NPDR/proliferative DR (PDR; n = 41). Male sex was significantly associated with smaller FAZ area/perimeter and lower DCP VLD in both non-diabetic subjects and patients with diabetes. Male sex in the diabetic group was additionally associated with lower SCP VD/VLD and DCP VD. Addition of an interaction between male sex and diabetes status in the interaction analysis showed that being male and diabetic conferred increased reduction in DCP VD and VLD compared to sex-based changes in non-diabetics. Larger FAZ perimeter, lower SCP VD/VLD, and lower DCP VLD were associated with poorer visual acuity in diabetics. CONCLUSIONS: On OCTA, male patients with diabetes may have more severe microvascular disease especially in the DCP compared to women. TRANSLATIONAL EVIDENCE: Sex-based alterations in diabetic microvascular disease has the potential to influence future basic and clinical studies as well as the implementation of OCTA disease markers.

PURPOSE: Early and intermediate non-neovascular AMD (NN-AMD) has the potential to progress to either advanced NN-AMD with geographic atrophy, or to neovascular AMD (N-AMD) with CNV. This exploratory study performed an unbiased analysis of aqueous humor transcriptome in patients with early or intermediate NN-AMD vs. treatment-naïve N-AMD to determine the feasibility of using this method in future studies investigating pathways and triggers for conversion from one form to another. METHODS: Aqueous humor samples were obtained from 20 patients with early or intermediate NN-AMD and 20 patients with untreated N-AMD, graded on clinical examination and optical coherence tomography. Transcriptome profiles were generated using next-generation sequencing methods optimized for ocular samples. Top-ranked transcripts were compared between groups, and pathway enrichment analysis was performed. RESULTS: Seventy-eight differentially expressed transcripts were identified. Unsupervised clustering of differentially expressed transcripts was able to successfully differentiate between the two groups based on aqueous transcriptome alone. Pathway analysis highlighted changes in expression of genes associated with mitochondrial respiration, oxidative stress, ubiquitination, and neurogenesis between the two groups. CONCLUSIONS: This pilot study compared the aqueous fluid transcriptome of patients with early or intermediate NN-AMD and untreated N-AMD. Differences in transcripts and transcriptome pathways identified in the aqueous of patients with early or intermediate NN-AMD compared with patients with N-AMD are consistent with those previously implicated in the pathogenesis of these distinct AMD subtypes. The findings from this exploratory study warrant further investigation using a larger, prospective study design, with the inclusion of a control group of eyes without AMD.

Meningiomas are the most common primary intracranial neoplasm. While traditionally viewed as benign, meningiomas are associated with significant patient morbidity, and certain meningioma subgroups display more aggressive and malignant behavior with higher rates of recurrence. Historically, the risk stratification of meningioma recurrence has been primarily associated with the World Health Organization histopathological grade and surgical extent of resection. However, a growing body of literature has highlighted the value of utilizing molecular characteristics to assess meningioma aggressiveness and recurrence risk. In this review, we discuss preclinical and clinical evidence surrounding the use of molecular classification schemes for meningioma prognostication. We also highlight how molecular data may inform meningioma treatment strategies and future directions.

Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. Enteroids generated from the developing human intestine grown in standard culture conditions, which contain EGF, are dominated by stem and progenitor cells and feature little differentiation and no spatial organization. Our results demonstrate that EREG can replace EGF in vitro, and EREG leads to spatially resolved enteroids that feature budded and proliferative crypt domains and a differentiated villus-like central lumen. Multiomic (transcriptome plus epigenome) profiling of native crypts, EGF-grown enteroids, and EREG-grown enteroids showed that EGF enteroids have an altered chromatin landscape that is dependent on EGF concentration, downregulate the master intestinal transcription factor CDX2, and ectopically express stomach genes, a phenomenon that is reversible. This is in contrast to EREG-grown enteroids, which remain intestine like in culture. Thus, EREG creates a homeostatic intestinal niche in vitro, enabling interrogation of stem cell function, cellular differentiation, and disease modeling.