Adjacent Choroid Research Articles

Shear-wave elastographic imaging in choroidal melanomas: clinical and hemodynamic correlations.

This study evaluated the role of shear wave elastography imaging (SWEΙ) in uveal melanomas and the associations between SWEI and clinical and hemodynamic findings. Prospective, clinical study METHODS: Twelve patients with uveal melanomas, scheduled to undergo Ru-106 brachytherapy, were prospectively recruited from the Department of Ophthalmology of the University Hospital of Heraklion (September-December 2022). B-mode, hemodynamic and SWEI ultrasonography examinations were performed with the HiScan (OPTIKON 2000) and the LOGIQ E9 (GE Healthcare) sonographic systems, respectively. Differences in SWEI scores (kPa) between tumor (TS) and adjacent non-affected choroid (CS), as well as between TS and orbital fat (FS) were examined. Correlations between SWEI and intra-tumoral hemodynamic parameters, including peak systolic and end diastolic velocities and resistivity index (RI) were also examined. TS was significantly correlated with intra-tumoral RI (Pearson's bivariate correlation coefficient 0.681, p=0.015) and with maximal tumor height (Pearson's bivariate correlation coefficient 0.620, p=0.031). TS was significantly higher than both FS and CS scores (paired-samples t-test, p=0.003 and p=0.006, respectively). SWEI score is applicable as a quantitative biomechanical marker in the assessment of choroidal melanoma. Choroidal melanomas are stiffer than both adjacent choroid and orbital fat. Moreover, choroidal melanomas with higher RI as well as those with higher apical elevations display higher SWEI scores.

Torpedo Maculopathy: Case Series of an Underdiagnosed and Rare Condition Using Multimodal Imaging.

Background: Torpedo maculopathy is a rare benign congenital anomaly of the retinal pigment epithelium (RPE) mostly asymptomatic throughout life. The clinical presentation is very typical displaying an ovoid cleft of the RPE typically located in the temporal zone of the macula. Despite this pathognomonic feature, patients are often referred to retina clinics for secondary opinions. The aim of this case series is to raise awareness of this rare condition among ophthalmologists and to explore the added value of multimodal imaging, in particular OCT angiography (OCTA), to increase its identification. History and Signs: 5 patients between 11 and 73 years-old were referred in our institution for further evaluation of an unilateral yellowish hypopigmented torpedo-shaped flat lesion in the temporal sector of the macula. Lesions varied in size and distance from the fovea. 3 patients were asymptomatic and 2 patients complained of decreased vision. Of these two, only one had a decrease in visual acuity in the affected eye as measured at the consultation. Therapy and Outcome: Spectral domain OCT (SD-OCT) revealed in all cases a thinned RPE combined with hyper-reflectivity of the adjacent choroid on the ovoid lesion while the foveal region remained normal. Infrared Reflectance showed a heterogeneous hyperreflective area deliminated with a hyporeflective ring. On fundus blue light autofluorescence (FAF) exam, the lesions appeared hypoautofluorescent with a hyperautofluorescent perimeter. In all cases, OCTA of torpedo lesions identified choriocapillary remodeling with different phenotypes reflecting a possible disappearance of the choriocapillary layer with window effect. The superficial and deep capillary plexus layers (SCP and DCP) were in most cases comparable to the adjacent retina, and no differences were found in the quantitative analysis of SCP and DCP vascular density measured in each eye. Conclusion: Torpedo maculopathy is a rare well described clinical condition that displays pathognomonic features on regular fundoscopy examination. Our case series showed that the use of multimodal imaging, including SD-OCT, FAF and OCTA, seems to be of little value in increasing its recognition thus confirming the importance of its typical clinical appearance among ophthalmologists. Interestingly, SD-OCT and OCTA demonstrated no abnormalities of the adjacent macula of the affected eye, which seems to confirm its isolated local unilateral ophthalmic condition.

Inner Choroidal Fibrosis: An Optical Coherence Tomography Biomarker of Severity in Chronic Central Serous Chorioretinopathy

To describe a potential biomarker termed as inner choroidal fibrosis in cases of chronic central serous chorioretinopathy (CSCR) presenting to a tertiary referral center. Observational case series. Five eyes of 4 patients with CSCR were noted to have a gray-white subretinal lesion in the macula, which was analyzed with multimodal imaging. The lesions were hypofluorescent on autofluorescence, fundus fluorescein angiography, and indocyanine angiography. In all cases, a characteristic heterogeneous, hyperreflective lesion in the inner choroid was seen on optical coherence tomography (OCT), corresponding to the white subretinal lesions. The lesion was distinct from the adjacent choroid, with greater reflectivity and greater thickness than the adjacent compressed choroidal vasculature. The dilated outer pachyvessels were pushed outward or sideways in all cases. On OCT-angiography, the corresponding lesion showed flow void areas. We have termed this zone of inner choroidal hyperreflectivity "inner choroidal fibrosis." Upon analyzing the clinical course, 3 of the patients had a history of choroidal neovascularization. The contralateral eye in 2 of these 3 patients also developed choroidal neovascularization. Three of the eyes had an overlying focal choroidal excavation. We report a potential biomarker of CSCR termed "inner choroidal fibrosis" in 4 cases of chronic CSCR. It can best be identified on enhanced depth or swept source OCT as a region of heterogeneous hyperreflectivity in the inner choroid. This fibrosis could be regarded as a degenerative process secondary to more severe disease in the past.

Elevated ZNF704 expression is associated with poor prognosis of uveal melanoma and promotes cancer cell growth by regulating AKT/mTOR signaling

BackgroundUveal melanoma (UM) is the most common intraocular malignancy in adults, with a poor survival prognosis. To date, limited understanding of UM’s molecular mechanisms constitutes an obstacle to developing effective therapy. In this study, we examined key regulators mediating UM progression and their clinical relevance.MethodsTranscriptomics of UM patients and cells were analyzed via RNA sequencing and bioinformatic analysis. Zinc finger protein 704 (ZNF704) was identified as prognosis-related biomarker for UM based on clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA). Gene expression was knocked down by specific shRNAs/siRNAs and overexpressed by transfection with plasmids inserted with investigated gene cDNA. Cell proliferation, viability and invasion abilities were determined by CCK8, colony formation and transwell assays, respectively. For cell cycle and apoptosis, cells were PI or PI/Annexin V-APC stained and analyzed by flow cytometry. Standard immunoblotting and quantitative RT-PCR were employed to assess the mRNA and protein abundance. To determine tumor growth in vivo, 4-week-old BALB/c-nu immune-deficient nude mice were inoculated with tumor cells.ResultsAnalysis of differential expressed genes (DEGs) and survival analysis identified ZNF704 as a novel biomarker of UM. Prognostic analysis indicated ZNF704 as an independent predictor of UM overall survival. Expression of ZNF704 is elevated in UM tissues relative to adjacent normal choroid tissues. Knockdown of ZNF704 suppressed the growth and migration of UM cells and vice versa. In addition, expression of ZNF704 arrest UM cells at G0/G1 phase and inhibit cell apoptosis. RNA sequencing analysis indicated that SORBS3 were dysregulated after ZNF704 downregulation. Gene Set Enrichment Analysis (GSEA) revealed that upon ZNF704 knowndown, genes related with PI3K/AKT/mTOR, EMT and metastasis are enriched. Mechanistically, ZNF704 activates AKT/mTOR/glycolysis signaling pathway in UM cells. Moreover, expression of SORBS3 is downregulated by ZNF704 and knockdown of SORBS3 restored tumor cell viability in ZNF704 silenced cells.ConclusionsZNF704 predicts poor prognosis of UM and exhibit pro-oncogenic effect in UM progression in vivo and in vitro, mediated through AKT/mTOR signaling pathway and suppression of SORBS3 expression.

OCT classification of choroidal nevi

The study aims to determine the types of OCT patterns of CN and to evaluate their prognostic value. The study included 50 patients with CN (53 nevi). The height of 19 nevi evaluated with ultrasonography was 1.33±0.43 mm, diameter - 5.47±1.68 mm. CN is an area of local increase in reflectivity of the choroid; its widening and elevation of the tomographic section were observed in 72% of nevi. In more than half of all cases a distinct hyperreflective border was revealed between the CN and adjacent choroid. In two thirds of all cases the choriocapillaris layer was preserved and visualized mainly along the edge of lesion. Analysis of OCT scans showed distinct differences, which allowed designation of four OCT types of CN: 1) nevi with typical OCT pattern; 2) nevi with changes in retinal pigment epithelium (RPE); 3) nevi with neuroepithelial detachment; 4) nevi with atypical OCT pattern. Based on the analysis of OCT images of the determined types of nevi, it can be assumed that all of them initially had typical OCT pattern. With enlargement of the nevi and increase in the duration of its presence in the choroid, dystrophic processes in the adjacent retina and changes in RPE begin to occur. Disturbed pumping ability of the damaged RPE results in disruption of the trophism of adjacent retina, which leads to development of atrophic changes. Nevi with atypical OCT pattern should be considered as a sign of long-term benign process in the choroid that will cause atrophic changes in the choroid and adjacent retina, while nevi with changes in RPE and with neuroepithelial detachment - as a risk factor for transition to choroidal melanoma.

Ocular Melanocytoma

Abstract Melanocytoma, also known as magnocellular nevus, most commonly occurs on the optic disk, sometimes involving the adjacent retina or choroid. It may be confused with malignant melanoma both clinically and histopathologically. Histopathologically, melanocytoma is composed of deeply pigmented, round to oval nevus cells without malignant features. Typically, melanocytoma is benign1 and shows a stationary course, although minor enlargement occurs in 10%–15% of cases. In rare cases, severe visual loss can result from tumor necrosis, compressive optic neuropathy, or malignant transformation, which occurs in 1%–2% of cases. Therefore, it is generally a benign lesion requiring minimal intervention but warrants lifetime follow-up.

High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota.

Relationships between retinal disease, diet, and the gut microbiome have started to emerge. In particular, high-fat diets (HFDs) are associated with the prevalence and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). These effects are thought to be partly mediated by the gut microbiome, which modulates interactions between diet and host homeostasis. Nevertheless, the effects of HFDs on the retina and adjacent retinal pigment epithelium (RPE) and choroid at the transcriptional level, independent of gut microbiota, are not well-understood. In this study, we performed the high-throughput RNA-sequencing of germ-free (GF) mice to explore the transcriptional changes induced by HFD in the RPE/choroid. After filtering and cleaning the data, 649 differentially expressed genes (DEGs) were identified, with 616 genes transcriptionally upregulated and 33 genes downregulated by HFD compared to a normal diet (ND). Enrichment analysis for gene ontology (GO) using the DEGs was performed to analyze over-represented biological processes in the RPE/choroid of GF-HFD mice relative to GF-ND mice. GO analysis revealed the upregulation of processes related to angiogenesis, immune response, and the inflammatory response. Additionally, molecular functions that were altered involved extracellular matrix (ECM) binding, ECM structural constituents, and heparin binding. This study demonstrates novel data showing that HFDs can alter RPE/choroid tissue transcription in the absence of the gut microbiome.

Magnetic Resonance Imaging Can Reliably Differentiate Optic Nerve Inflammation from Tumor Invasion in Retinoblastoma with Orbital Cellulitis

To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion. A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case-control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls. A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis. In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case-control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons. Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed. The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P < 0.001), and a larger eye size (P= 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16-52) to 89% (95% CI, 72-98). Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes.

Compensating for choroid plexus based off-target signal in the hippocampus using 18F-flortaucipir PET

Purpose: The hippocampus is affected by tau pathology early in Alzheimer's disease (AD) development. Accurate quantification of hippocampal tau signal using the tau-PET tracer 18F-flortaucipir is complicated, however, by off-target binding in the adjacent choroid plexus. We here present a new method for compensating for this off-target choroid plexus signal.Methods: As off-target binding in the choroid plexus is known to be higher using 18F-flortaucipir compared to 18F-RO948, we created a binary hippocampal mask in template space where 18F-flortaucipir signal was higher than 18F-RO948, using data from 30 patients that underwent both 18F-flortaucipir and 18F-RO948 PET. This mask, presumably representing hippocampal voxels affected by off-target binding from the choroid plexus, was then converted to native space and applied as an exclusion mask to 145 patients across the AD-spectrum scanned with 18F-flortaucipir. As an alternative approach exclusion masks were generated by expanding the choroid plexus ROI in native space. Results were analysed both without and with partial volume error correction (non-PVEc/PVEc).Results: Unmasked hippocampal standardized uptake value ratios (SUVR) were significantly correlated to choroid plexus SUVRs using both non-PVEc (p < 0.001, r = 0.28) and PVEc data (p < 0.05, r = 0.18). After applying the mask, however, these correlations disappeared. The diagnostic accuracy in separating cognitively impaired (CI) from cognitively unimpaired (CU) subjects improved after masking, from an AUC of 0.792 (95% C.I.,0.715–0.869) to 0.837 (95% C.I.,0.768–0.906) for non-PVEc data (p < 0.001), and from 0.798 (95% C.I.,0.722–0.873) to 0.834 (95% C.I.,0.766–0.903) for PVEc data (p < 0.001). The correlations to memory improved significantly for MMSE for unmasked vs. masked data both without (r = −0.440 vs. r = −0.499, p < 0.001) and with (r = −0.454 vs. r = −0.503, p < 0.001) PVEc. Similar results were found using the ADAS-Cog Delayed Word Recall test.Conclusion: Choroid plexus off-target binding interferes with the estimation of true hippocampal retention using 18F-flortaucipir PET. Using a mask to correct for this off-target signal, we improved the diagnostic accuracy of 18F-flortaucipir in the hippocampus and the correlation between 18F-flortaucipir hippocampal SUVR and cognitive measures.

Optical Coherence Tomography Characteristics of the Choroid Underlying Congenital Hypertrophy of the Retinal Pigment Epithelium

Purpose: This study evaluates and characterizes the choroid underlying congenital hypertrophy of the retinal pigment epithelium (CHRPE). Methods: Retrospective observational study of CHRPE at least 2 mm in diameter. Choroidal vascular architecture was qualitatively examined. Choroidal thickness was measured by 2 independent observers using enhanced depth imaging spectral domain optical coherence tomography. Results: Forty-six eyes of 46 patients with CHRPE were included. Thirty-two lesions had imaging sufficient for analysis. Haller’s layer was healthy in 18 (56%), thin in 13 (41%), and absent in 1 (2%). Sattler’s layer was atrophic in 30 (94%), and choriocapillaris was atrophic in 31 (97%). CHRPE with thinned Haller’s layer had significantly larger diameter. The mean sub-CHRPE choroidal thickness was 82.4 ± 7.9 µm, compared to a thickness of 148.4 ± 9.6 µm in the normal adjacent choroid (p < 0.0001). Mean retinal thickness overlying the CHRPE was 77.3 ± 4.3 µm, compared to a retinal thickness of 137.8 ± 2.9 µm overlying the normal adjacent choroid (p < 0.0001). Sub-CHRPE choroidal thickness was a mean of 56.2 ± 3.1% of the adjacent normal choroidal thickness. Conclusion: The underlying choroid CHRPE is thinner than the adjacent normal choroid. All layers of the choroid can be thin with a preference of the inner Sattler’s and choriocapillaris layers.

Anterior Optic Nerve Head Perfusion is Dependent on Adjacent Parapapillary Choroidal perfusion

Recent studies reported that parapapillary microvascular dropout (MvD) was significantly associated with glaucoma and glaucoma progression. To understand the clinical relevance/importance of MvD, it is essential to know the exact vascular anatomy of optic nerve head (ONH). Although it is known that parapapillary choroid and the deep ONH structure including prelaminar tissue are both supplied by branches of short posterior ciliary artery, it remains controversial whether parapapillary choroid provides a major contribution to the prelaminar tissue perfusion. This study investigated perfusion within and around the ONH using indocyanine green angiography. Thirty-three eyes from 33 patients with primary open-angle glaucoma and 10 eyes from 10 normal subjects were included. The temporal sequence of dye appearance in various tissues was analyzed. We also sought the microvessels directly responsible for blood supply to the prelaminar tissue. The perfusion of the prelaminar tissue, which occurred in a sectoral fashion, was dependent on the dye appearance in the adjacent parapapillary choroid. In addition, microvessels crossing over the optic disc margin from the parapapillary choroid to the ONH were found. The findings suggest that the centripetal flow from the parapapillary choroid is an important source of prelaminar tissue perfusion.

Transgenic increase in the β-endorphin concentration in cerebrospinal fluid alleviates morphine-primed relapse behavior through the μ opioid receptor in rats.

BackgroundOpioid‐primed relapse is a global burden. Although current strategies have improved, optimal therapy is urgently needed.MethodsA recombinant adenovirus (Ad‐NEP) expressing β‐endorphin (β‐EP) was designed and injected intracerebroventricularly (icv) into the right lateral ventricle in rats. Spatial and temporal β‐EP expression in the lateral ventricle wall, subventricular zone and adjacent choroid plexus and the β‐EP concentration in the cerebrospinal fluid (CSF) were observed during a 21‐day period. A morphine priming‐induced conditioned place preference (CPP) rat model was established. The β‐EP‐ir neuron counts, CSF β‐EP concentration, and CPP score, which were used to evaluate morphine‐primed reinstatement following extinction, were recorded 7 days after the icv injection. Additionally, the rats were pretreated with the irreversible μ opioid receptor antagonist β‐funaltrexamine (β‐FNA) and the selective κ opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) to identify the receptor‐dependent mechanism.ResultsBoth peak β‐EP expression in target neurons and the peak CSF β‐EP concentration occurred 7 to 8 days after Ad‐NEP icv injection. The sustainable increase in the CSF β‐EP concentration was correlated with a decrease in the CPP score 7 days after the Ad‐NEP icv injection. Furthermore, reinstatement was almost reversed by β‐FNA pretreatment 24 hours before the behavioral test, but nor‐BNI had little effect.ConclusionThe increasing cerebrospinal fluid β‐endorphin concentrations showed that the therapeutic effect on opioid relapse occurred predominantly through a μ opioid receptor‐dependent mechanism. The Ad‐NEP adenovirus can be considered an alternative therapy for opioid relapse.

Melanocytoma of the optic disk: A review.

Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina or choroid. Historically, this tumor was often confused with malignant melanoma both clinically and histopathologically. Today, however, it is generally recognized by its typical clinical features that differ from most melanomas and erroneous enucleation is rarely done. Histopathologically, melanocytoma is composed of intensely pigmented round to oval nevus cells with benign features. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10--15% of cases and can cause minor visual loss by a variety of mechanisms. In rare instance, it can induce severe visual loss due to spontaneous necrosis of the lesion or compressive optic neuropathy. More importantly, it can exhibit malignant transformation into melanoma in 1--2% of cases. Ophthalmologists should be familiar with melanocytoma of the optic disk and affected patients should be followed periodically.

Pax6 regulation of Sox9 in the mouse retinal pigmented epithelium controls its timely differentiation and choroid vasculature development.

The synchronized differentiation of neuronal and vascular tissues is crucial for normal organ development and function, although there is limited information about the mechanisms regulating the coordinated development of these tissues. The choroid vasculature of the eye serves as the main blood supply to the metabolically active photoreceptors, and develops together with the retinal pigmented epithelium (RPE). Here, we describe a novel regulatory relationship between the RPE transcription factors Pax6 and Sox9 that controls the timing of RPE differentiation and the adjacent choroid maturation. We used a novel machine learning algorithm tool to analyze high resolution imaging of the choroid in Pax6 and Sox9 conditional mutant mice. Additional unbiased transcriptomic analyses in mutant mice and RPE cells generated from human embryonic stem cells, as well as chromatin immunoprecipitation and high-throughput analyses, revealed secreted factors that are regulated by Pax6 and Sox9. These factors might be involved in choroid development and in the pathogenesis of the common blinding disease: age-related macular degeneration (AMD).

Multiple pathological mechanisms contribute to hippocampal damage in the experimental autoimmune encephalomyelitis model of multiple sclerosis.

Emotional and cognitive deficits and associated hippocampal damage observed in multiple sclerosis (MS) are now recognized as primary disease manifestations. However, the pathological substrate of these dysfunctions is unclear. In the experimental autoimmune encephalomyelitis (EAE) MS model, impaired hippocampal-dependent functions are concomitant with severe microglial reactivity and neurodegeneration, but reports vary with respect to evidence of lymphocytic infiltration, raising questions as to the nature of the underlying neurodegenerative mechanisms. Our investigations of EAE-induced inflammation across the hippocampal formation showed CD3 infiltration only in regions adjacent to inflamed meningeal membranes interposed between the ventral aspect of the hippocampus and the dorsal aspect of the mid-brain, but widespread microglial reactivity across the structure. Regions that contact the lateral ventricles do not show inflammation, but CD3 cells are observed in the adjacent ventricular space and choroid plexus, suggesting that microglial reactivity in these regions results from exposure to proinflammatory mediators released into the ventricles. These data indicate that multiple pathophysiological mechanisms underlie hippocampal damage during EAE. Treatment with the immunomodulator FTY720 eliminates microglial reactivity across the whole structure, suggesting potential benefit for neuropsychological symptoms in MS.

Residual deformations in ocular tissues.

Residual deformations strongly influence the local biomechanical environment in a number of connective tissues. The sclera is known to be biomechanically important in healthy and diseased eyes, such as in glaucoma. Here, we study the residual deformations of the sclera, as well as the adjacent choroid and retina. Using freshly harvested porcine eyes, we developed two approaches of quantifying residual deformations in the spherically shaped tissues of interest. The first consisted of punching discs from the posterior wall of the eye and quantifying the changes in the area and eccentricity of these samples. The second consisted of cutting a ring from the equatorial sclera and making stress-relieving cuts in it. Measurements of curvature were made before and after the stress-relieving cuts. Using the first approach, we observed a 42% areal contraction of the choroid, but only modest contractions of the sclera and retina. The observed contractions were asymmetric. In the second approach, we observed an opening of the scleral rings (approx. 10% decrease in curvature). We conclude that residual bending deformations are present in the sclera, which we speculate may be due to radially heterogeneous growth and remodelling of the tissue during normal development. Further, residual areal deformations present in the choroid may be due to the network of elastic fibres in this tissue and residual deformations in the constituent vascular bed. Future studies of ocular biomechanics should attempt to include effects of these residual deformations into mechanical models in order to gain a better understanding of the biomechanics of the ocular wall.

Bevacizumab for the treatment of a complicated posterior melanocytoma

PurposeTo present a case of a complicated posterior melanocytoma that was successfully treated with intravitreal bevacizumab.Case reportA 50-year-old Caucasian man was referred with sudden-onset metamorphopsia and decreased vision in his right eye over the course of the last 2 months. His best-corrected visual acuity was 20/80 and poorer than Jaeger 14 in the right eye, and 20/20 and Jaeger 1 in his left eye. In the right fundus, there was a melanocytic lesion occupying the inferotemporal quadrant of the optic disk, extending to the adjacent choroid inferiorly; optic nerve edema, superotemporal retinal vein dilatation, and subretinal fluid under the macula and nasal half of the posterior pole were observed, and a subretinal choroidal neovascularization complex was observed adjacent to the superotemporal margin of the optic disk, confirmed by fluorescein angiography, surrounded by a dense subretinal hemorrhage. Optical coherence tomography showed retinal edema and detachment of neurosensory retina. The patient was treated with three consecutive doses on a monthly basis of intravitreal 1.25 mg/0.05 mL bevacizumab. Visual acuity recovered rapidly, and at 4 months after treatment, it was 20/20 and Jaeger 1, with complete resolution of macular edema and subretinal fluid and hemorrhage. After 3 years of follow-up, best-corrected visual acuity remained stable, macular area was normal, and there was no evident optic nerve edema, retinal vein caliber and aspect were normal, and there was no significant change of the tumor. Fluorescein angiography only evidenced late staining of choroidal neovascularization scar, and optical coherence tomography showed a normal macular anatomy.ConclusionIntravitreal bevacizumab was effective in the treatment of choroidal neovascularization, optic nerve edema, venous dilatation, and local capillary telangiectasia, complicating an optic disk melanocytoma.

67.: Posterior choroidal artery stroke with infarction of choroid plexus: A rare manifestation of a common entity

Posterior choroidal artery (PChA) infarction is a thalamic infarct syndrome with specific radiological and clinical findings. The posterior choroidal artery has two main divisions, lateral and medial. We describe two patients with PChA infarction who presented with symptoms initially suggestive of anterior circulation ischaemia. Patient 1 is a 64-year-old right-handed man who presented with right-sided weakness, paraesthesia and a 24 h history of word finding difficulty which spontaneously resolved. MRI with diffusion weighted imaging (DWI) demonstrated acute infarcts involving the pulvinar of left thalamus and adjacent choroid plexus, and periventricular white matter adjacent to the left lateral ventricle. Patient 2 is a 57-year-old right-handed man with right upper and lower limb clumsiness and altered sensation. Subsequent MRI with DWI demonstrated an area of infarction affecting the sub-ependymal region along the lateral aspect of the left lateral ventricle, and approximating the posterior body and tail of the caudate nucleus. PChA infarction is rare due to multiple anastamoses. Choroid plexus infarcts are usually clinically silent. There have only been a few reported cases of choroid plexus infarction. We describe two patients with lateral PChA infarction. This is a rare stroke syndrome due to multiple anastamotic connections and produces interesting radiological findings, particularly that of choroid plexus infarction. PChA infarction has variable clinical presentations and can mimic an anterior circulation stroke.

Ocular histiocytic sarcoma in a cat

A 13-year-old male neutered British blue cat presented with uveitis, hyphema, and dyscoria in the right eye. Light microscopic examination revealed that the ciliary body, iris root, drainage angle, and adjacent choroid were infiltrated by sheets of large neoplastic mononuclear and multinucleate round to polygonal cells. Neoplastic cells stained immunopositive for CD18 and HLA-DR (MHC class II) and were immunonegative for CD3, CD79a, MUM-1, CD117 (c-Kit), and S100. These findings were consistent with a histiocytic sarcoma. The cat later developed multiple cutaneous masses composed of a similar neoplastic cell population to that seen in the eye. Eight months following enucleation, the cat developed respiratory distress and was euthanized. Postmortem examination revealed multiple pulmonary tumors associated with a pleural effusion.

IGF-II Promotes Stemness of Neural Restricted Precursors

Insulin-like growth factor (IGF)-I and IGF-II regulate brain development and growth through the IGF type 1 receptor (IGF-1R). Less appreciated is that IGF-II, but not IGF-I, activates a splice variant of the insulin receptor (IR) known as IR-A. We hypothesized that IGF-II exerts distinct effects from IGF-I on neural stem/progenitor cells (NSPs) via its interaction with IR-A. Immunofluorescence revealed high IGF-II in the medial region of the subventricular zone (SVZ) comprising the neural stem cell niche, with IGF-II mRNA predominant in the adjacent choroid plexus. The IGF-1R and the IR isoforms were differentially expressed with IR-A predominant in the medial SVZ, whereas the IGF-1R was more abundant laterally. Similarly, IR-A was more highly expressed by NSPs, whereas the IGF-1R was more highly expressed by lineage restricted cells. In vitro, IGF-II was more potent in promoting NSP expansion than either IGF-I or standard growth medium. Limiting dilution and differentiation assays revealed that IGF-II was superior to IGF-I in promoting stemness. In vivo, NSPs propagated in IGF-II migrated to and took up residence in periventricular niches while IGF-I-treated NSPs predominantly colonized white matter. Knockdown of IR or IGF-1R using shRNAs supported the conclusion that the IGF-1R promotes progenitor proliferation, whereas the IR is important for self-renewal. Q-PCR revealed that IGF-II increased Oct4, Sox1, and FABP7 mRNA levels in NSPs. Our data support the conclusion that IGF-II promotes the self-renewal of neural stem/progenitors via the IR. By contrast, IGF-1R functions as a mitogenic receptor to increase precursor abundance.