Long-Term Outcomes of Vitrectomy for Idiopathic Epiretinal Membrane With Internal Limiting Membrane Removal in Patients With Good Preoperative Visual Acuity.

Purpose: To evaluate the long-term visual results of vitrectomy with epiretinal membrane (ERM) and internal limiting membrane (ILM) removal for idiopathic ERM in eyes with a preoperative visual acuity (VA) of 20/50 or better. Methods: This retrospective review of a consecutive case series comprised 337 patients. Of these, 36 eyes of 36 patients had ERM and ILM removal from 2017 to 2018. Inclusion criteria included a subjective decrease in VA, a preoperative VA of 20/50 or better, vitrectomy with ERM and ILM removal for ERM, and a minimum 6-month follow-up. Paired t tests were used to determine the statistical significance (P < .05) of VA changes postoperatively. Results: The mean (±SD) best-corrected logMAR VA improved to a maximum of 0.125 ± 0.09 (Snellen equivalent 20/26.4) at a mean of 11.1 months postoperatively (P < .001). The VA continued to significantly improve over the long term (mean, 41.6 months; range, 6-63; P < .001). Overall long-term data trended heavily toward VA improvement (25/36 patients [69.4%]) and stability (10/36 patients [27.7%)] after ERM and ILM removal, with only 1 patient (2.8%) having worse VA. There were no intraoperative or postoperative complications related to ERM and ILM removal. Conclusions: Surgery to remove idiopathic ERM and ILM for patients with significant symptoms and good preoperative VA may result in excellent long-term visual results.

Pembrolizumab-Induced Nodular Posterior Scleritis.

Purpose: To report a case of painless posterior scleritis presenting as a choroidal nodule in a patient with history of a tumor being treated with pembrolizumab. Methods: A case and its findings were analyzed, and a relevant literature review was performed. Results: A 20-year-old woman with a history of ependymoma presented with painless blurred vision in the right eye after being started on pembrolizumab for a tumor recurrence. Fundoscopy showed a solitary amelanotic choroidal lesion with surrounding subretinal fluid in the affected eye. Ultrasonography showed moderate internal reflectivity and fluid in Tenon capsule consistent with nodular posterior scleritis. After a course of systemic steroids and discontinuation of the pembrolizumab, the choroidal lesion completely resolved. Conclusions: Clinicians should be aware of posterior scleritis as an ocular complication of this class of medications.

Visual outcomes of macula-involving rhegmatogenous retinal detachment in patients with and without age-related macular degeneration.

BACKGROUND: The prognosis for patients with macula-off rhegmatogenous retinal detachment (RRD) and concomitant age-related macular degeneration (AMD) is not well known. The purpose of this study is to compare visual outcomes in macula-off RRD in eyes with AMD versus a group of comparison eyes without AMD. METHODS: This was a retrospective chart review of 1149 patients. A total of 191 eyes met study criteria, 162 non-AMD eyes (controls), and 29 AMD eyes. The main outcome measure was postoperative visual acuity following pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV/SB in control eyes versus AMD eyes. This was compared using Fisher's exact test. RESULTS: There was a statistically significant difference in postoperative visual acuity by AMD status, with those without AMD having a worse visual outcome overall (p = 0.0048). A similar percentage of AMD versus non-AMD eyes achieved vision better than 20/40. More patients in the non-AMD group achieved a final visual acuity between 20/40 and 20/200. Of patients with AMD, more had vision worse than 20/200 though 58% maintained functional vision (better than 20/200). Those without AMD had a higher frequency of Count Fingers (CF), Hand Motion (HM), Light Perception (LP), or No Light Perception (NLP) vision (p = 0.023). CONCLUSIONS: Though postoperative visual acuity was worse overall in the non-AMD group with a higher frequency of patients having final vision of CF, HM, LP, or NLP, this is likely a function of the difference in sample size and composition between the two groups. Importantly, this study suggests AMD patients can expect similar outcomes to non-AMD patients after RRD repair. We conclude that AMD patients can achieve functional vision after RRD surgery, similar to those without AMD.

Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression.

The cerebral cortex contains an enormous number of neurons, allowing it to perform highly complex neural tasks. Understanding how these neurons develop at the correct time and place and in accurate numbers constitutes a major challenge. Here, we demonstrate a novel role for Gli3, a key regulator of cortical development, in cortical neurogenesis. We show that the onset of neuron formation is delayed in Gli3 conditional mouse mutants. Gene expression profiling and cell cycle measurements indicate that shortening of the G1 and S phases in radial glial cells precedes this delay. Reduced G1 length correlates with an upregulation of the cyclin-dependent kinase gene Cdk6, which is directly regulated by Gli3. Moreover, pharmacological interference with Cdk6 function rescues the delayed neurogenesis in Gli3 mutant embryos. Overall, our data indicate that Gli3 controls the onset of cortical neurogenesis by determining the levels of Cdk6 expression, thereby regulating neuronal output and cortical size.

Vitrectomy and Vitrector Port Needle Biopsy of Choroidal Melanoma for Gene Expression Profile Testing Immediately before Brachytherapy.

PURPOSE: Transvitreal and transscleral needle biopsy can result in complications including vitreous hemorrhage and retinal detachment. This study evaluated a technique using 25-gauge vitrectomy as an adjunct to needle biopsy immediately before brachytherapy to minimize these complications and preserve good visual acuity. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-seven consecutive eyes of 57 patients with treatment-naïve medium choroidal melanomas without extraocular extension from July 2012 through September 2015. METHODS: Fifty-seven consecutive eyes of 57 patients with a clinically diagnosed choroidal melanoma underwent complete 25-gauge posterior vitrectomy followed by transvitrector port fine-needle aspiration biopsy of the tumor immediately before implantation of a radioactive iodine 125 plaque as treatment for the tumor. Cytopathologic analysis was not performed on the tumor aspirates in this study. MAIN OUTCOME MEASURES: Best-corrected postoperative visual acuity, postoperative complications of the reported technique, implantation tumor development, local tumor recurrence, presence of metastatic disease after surgery, and sufficiency of the tumor aspirates obtained by the reported technique for successful gene expression profile testing and prognostic classification. RESULTS: Mean preoperative and postoperative visual acuities were similar (20/60 vs. 20/80, respectively). Mean tumor thickness was 5.0 mm (range, 2.5-10 mm) and mean tumor basal diameter was 13.1 mm (range, 7-22 mm). Only 1 of 57 eyes (1.8%) showed a transient vitreous hemorrhage, biopsy yield was 100% for genetic analysis, and no patients showed recurrence or implantation tumor at the vitrector site. CONCLUSIONS: Combined 25-gauge posterior vitrectomy and 25-gauge trans-vitrector port needle aspiration biopsy immediately before brachytherapy is excellent for obtaining tumor aspirate for gene expression profiling while controlling for hemostasis, resulting in few complications.

Outcomes of Choroidal Melanoma 25-Gauge Vitrectomy Needle Biopsy and Iodine 125 Brachytherapy Performed by Directly Supervised Fellows versus Attending Faculty.

PURPOSE: To evaluate the outcomes of choroidal melanoma 25-gauge vitrectomy needle biopsy and iodine 125 (125I) brachytherapy performed by supervised fellows compared with experienced faculty. DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixty-three consecutive eyes of 63 patients with treatment-naïve medium choroidal melanomas without extraocular extension. METHODS: Sixty-three consecutive eyes of 63 patients undergoing simultaneous 125I brachytherapy and 25-gauge vitrectomy melanoma biopsy for choroidal melanoma. One attending surgeon performed 31 surgeries and 2 fellows performed 32 surgeries. All cases treated by fellows were under direct supervision of the attending physician. MAIN OUTCOME MEASURES: Percentage of adequate biopsy sample, tumor regression, and postoperative complications. RESULTS: There were no baseline differences between the groups. The biopsy yield for gene expression profile and the melanoma regression rate were equal in both groups (63/63 [100%]; P = 1.0). Complications occurred in 1 of 31 faculty surgery patients (transient vitreous hemorrhage) and in 0 of 32 fellow surgery patients (P = 1.0). CONCLUSIONS: With proper supervision, fellows can achieve equally high biopsy yield and melanoma regression rate with few complications compared with experienced faculty.

BILATERAL ISOLATED CHOROIDAL MELANOCYTOSIS.

PURPOSE: To report a very rare case of bilateral isolated choroidal melanocystosis. METHODS: Clinical case report and literature review. RESULTS: A 24-year-old asymptomatic African American woman presented with bilateral diffuse choroidal pigmentation. The diagnosis of bilateral isolated choroidal melanocytosis was made, and optical coherence tomography was remarkable for increased choroidal thickness with a normal inner and outer retina. CONCLUSION: Although extremely rare, bilateral isolated choroidal melanocytosis may occur in young patients, as well as in those who are African American. Longer follow-up of this case and those in the literature will elucidate whether these choroidal lesions enlarge or have a risk of developing uveal melanoma.

VITREORETINAL SURGICAL OUTCOMES PERFORMED BY SUPERVISED RETINAL FELLOWS VERSUS ATTENDING FACULTY SURGEONS.

PURPOSE: To evaluate common vitreoretinal surgeries performed by retinal fellows under direct faculty supervision, compared with experienced faculty members. METHODS: Retrospective study analyzing 592 consecutive eyes undergoing retinal surgery from 2009 to 2011 at Retina Consultants of Alabama/University of Alabama at Birmingham, Department of Ophthalmology. Vitreoretinal surgeries included macular hole, macular pucker, retinal detachment, diabetic vitreous hemorrhage, and diabetic tractional retinal detachment. Three fellows performed 390 cases (divided into first or second year fellows), while 4 faculty members performed 202 cases. All 390 fellow-performed cases were under direct supervision. Chi-square analysis was used to compare outcomes. RESULTS: There were no baseline differences between the groups. The mean postoperative visual improvement was statistically significant and equal in all groups, as well as between each physician (P ≤ 0.0001). Complications occurred in 29/592 cases (4.8%), whereas reoperations occurred in 21/592 cases (3.5%) and were equally distributed across groups. There were no differences in complications and reoperations when comparing first-year with second-year fellows. CONCLUSION: With proper supervision, vitreoretinal fellows can achieve an equally high visual improvement with low complication and reoperation rates compared with experienced faculty. The year of fellowship does not significantly influence outcomes or complications. Quality outcomes after vitreoretinal surgery can be obtained throughout fellowship training.

Cerebral Cortex Expression of Gli3 Is Required for Normal Development of the Lateral Olfactory Tract.

Formation of the lateral olfactory tract (LOT) and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. Gli3 null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for Gli3 in its development. Here, we used Emx1Cre;Gli3fl/fl conditional mutants to investigate LOT formation and colonization of the olfactory cortex in embryos in which loss of Gli3 function is restricted to the dorsal telencephalon. These mutants form an olfactory bulb like structure which does not protrude from the telencephalic surface. Nevertheless, mitral cells are formed and their axons enter the piriform cortex though the LOT is shifted medially. Mitral axons also innervate a larger target area consistent with an enlargement of the piriform cortex and form aberrant projections into the deeper layers of the piriform cortex. No obvious differences were found in the expression patterns of key guidance cues. However, we found that an expansion of the piriform cortex temporally coincides with the arrival of LOT axons, suggesting that Gli3 affects LOT positioning and target area innervation through controlling the development of the piriform cortex.

Evaluation of proliferating cell abundance and phenotypes in proliferative diabetic retinopathy.

BACKGROUND: The aim of this work is to evaluate the abundance, origins, and phenotypes of actively proliferating cells in proliferative diabetic retinopathy (PDR). METHODS: Eleven epiretinal membranes from patients undergoing surgery for PDR were evaluated by indirect immunofluorescence for evidence of cell proliferation using the nuclear cell proliferation marker Ki67 and for cell identities using glial fibrillary acidic protein (GFAP), glutamine synthetase, and α-smooth muscle actin (αSMA). RESULTS: Ki67 positivity was consistently rare in PDR epiretinal membranes at 3.02 ± 1.42 % of the total cell population. The majority of the Ki67-positive cells were also positive for GFAP (74.0 %) with lower proportions positive for αSMA (30.7 %) and glutamine synthetase (1.5 %). Co-localization studies using glial and myoid markers revealed that virtually all (92 %) of the αSMA-positive cells are also GFAP positive and thus derive from glia. CONCLUSIONS: Entry into cell cycle and thus cell proliferation appears to be a rare phenomenon in PDR involving only a small percentage of the total cell population. Glia and/or glial-derived myofibroblasts appear to be the predominate cell types in epiretinal scar tissues and also account for the majority of the actively proliferating cells.

Expansion of the piriform cortex contributes to corticothalamic pathfinding defects in Gli3 conditional mutants.

The corticothalamic and thalamocortical tracts play essential roles in the communication between the cortex and thalamus. During development, axons forming these tracts have to follow a complex path to reach their target areas. While much attention has been paid to the mechanisms regulating their passage through the ventral telencephalon, very little is known about how the developing cortex contributes to corticothalamic/thalamocortical tract formation. Gli3 encodes a zinc finger transcription factor widely expressed in telencephalic progenitors which has important roles in corticothalamic and thalamocortical pathfinding. Here, we conditionally inactivated Gli3 in dorsal telencephalic progenitors to determine its role in corticothalamic tract formation. In Emx1Cre;Gli3(fl/fl) mutants, only a few corticothalamic axons enter the striatum in a restricted dorsal domain. This restricted entry correlates with a medial expansion of the piriform cortex. Transplantation experiments showed that the expanded piriform cortex repels corticofugal axons. Moreover, expression of Sema5B, a chemorepellent for corticofugal axons produced by the piriform cortex, is similarly expanded. Finally, time course analysis revealed an expansion of the ventral pallial progenitor domain which gives rise to the piriform cortex. Hence, control of lateral cortical development by Gli3 at the progenitor level is crucial for corticothalamic pathfinding.

Nonsupine positioning is preferred by patients over face-down positioning and provides an equivalent closure rate in 25- and 23-gauge macular hole surgery.

PURPOSE: Strict face-down positioning after macular hole surgery is very difficult for most patients. Our study seeks to determine if alleviated positioning (avoidance of supine positioning) has equivalent successful closure rates when compared with face-down positioning. A patient survey was also performed to determine patient preference. METHODS: A single-center retrospective review of patients undergoing macular hole repair with a questionnaire completed by each patient after air bubble clearance summarizing the two postoperative scenarios. Patients were asked which positioning strategy they would choose if they were having repeat surgery. Eighty-two patients undergoing pars plana vitrectomy with primary full-thickness macular hole repair were identified. Repair was performed with either 3 days of strict face-down positioning (57 of 82 patients) or with the avoidance of supine positioning (25 of 82 patients) but no required face-down positioning. RESULTS: The anatomical success rates were similar between the 2 groups with 96% of final hole closure (55/57) in the face-down group versus 100% (25/25) in the nonsupine group. Macular hole size appeared to be similar between the 2 groups (a mean of 408 µm in face-down group vs. that of 483 µm in nonsupine group, with a median of 400 in both groups). Patient preference was in favor of less stringent nonsupine postoperative requirements. Although 100% (25/25) of the nonsupine group would opt for the same strategy with repeat surgery, only 51% (29/57) of the face-down group would opt for face-down positioning with repeat surgery (P < 0.001). CONCLUSION: This study demonstrates equivalent closure rates among the patients who were assigned nonsupine versus face-down positioning postoperatively for macular hole repair, and that most patients would prefer to avoid strict face-down positioning if reoperated.

Traumatic lens subluxation presenting as pseudomelanoma.

An 82-year-old white man was referred for a suspected inferior pigmented, choroidal melanoma in his left eye. The patient stated that his left eye had been hit by a tree branch approximately 40 years prior, and he had not been able to see with it since then. Dilated fundus examination revealed a 14 × 8 mm dark, dome-shaped choroidal mass located inferiorly. Transillumination of the eye revealed no defects. Ultrasonography revealed a hollow lesion, consistent with a senile, dark dislocated cataract.

Safety, efficacy, and quality of life following sutureless vitrectomy for symptomatic vitreous floaters.

PURPOSE: To determine the safety, efficacy, and quality of life improvement following sutureless 25-gauge pars plana vitrectomy for symptomatic floaters. METHODS: Patients with symptomatic vitreous floaters who underwent sutureless vitrectomy between January 2008 and January 2011 were included. Data were collected regarding baseline preoperative characteristics, postoperative outcomes, complications, and a nine-item quality-of-life survey completed by each patient. RESULTS: One hundred and sixty-eight eyes (143 patients) underwent sutureless 25-gauge pars plana vitrectomy for symptomatic vitreous floaters. Mean Snellen visual acuity was 20/40 preoperatively and improved to 20/25 postoperatively (P < 0.0001). Iatrogenic retinal breaks occurred in 12 of 168 eyes (7.1%). Intraoperative posterior vitreous detachment induction was not found to increase the risk of retinal breaks (P = 1.000). Postoperative complications occurred in three eyes, of which one had transient cystoid macular edema and two had transient vitreous hemorrhage. Approximately 88.8% of patients completed a quality-of-life survey, which revealed that 96% were "satisfied" with the results of the operation, and 94% rated the experience as a "complete success." CONCLUSION: Sutureless 25-gauge pars plana vitrectomy for symptomatic vitreous floaters improved visual acuity, resulted in a high patient satisfaction quality-of-life survey, and had a low rate of postoperative complications. Sutureless pars plana vitrectomy should be considered as a viable means of managing patients with symptomatic vitreous floaters.

Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses.

OBJECTIVE: Assess current clinical practices for uveal melanoma (UM) and the impact of molecular prognostic testing on treatment decisions. DESIGN: Cross-sectional survey and sequential medical records review. PARTICIPANTS: Ophthalmologists who treat UM. METHODS: (A) Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B) 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014. MAIN OUTCOME MEASURES: Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms), and Fisher's exact test. Descriptive presentation of essay answers. RESULTS: The review of Medicare medical records included 191 evaluable patients, 88 (46%) with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP) Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1). There were 36 (19%) with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1). Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM patients. The majority of respondents (82%) performed molecular analysis of UM tumors after fine needle biopsy (FNAB); median: 15 FNAB per year; 2014 survey: 35 respondents with an annual median of 30 new UM patients. The majority offered molecular analyses of UM tumor samples to most patients. Patients with low metastatic risk (disomy 3 or GEP Class 1) were generally assigned to less frequent (every 6 or 12 months) and less intensive clinical visits. Patients with high metastatic risk (monosomy 3 or GEP Class 2) were assigned to more frequent surveillance with hepatic imaging and liver function testing every 3-6 months. High-risk patients were considered more suitable for adjuvant treatment protocols. CONCLUSION: The majority of ophthalmologists treating UM have adopted molecular diagnostic tests for the purpose of designing risk-appropriate treatment strategies.

Pax6 exerts regional control of cortical progenitor proliferation via direct repression of Cdk6 and hypophosphorylation of pRb.

The mechanisms by which early spatiotemporal expression patterns of transcription factors such as Pax6 regulate cortical progenitors in a region-specific manner are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6⁺/⁺ and Pax6⁻/⁻ cortices and identified many negatively regulated cell-cycle genes, including Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes that directly promote the mechanics of the cell cycle, and we found that Pax6 inhibits pRb phosphorylation and represses genes involved in DNA replication. Our results indicate that Pax6's modulation of cortical progenitor cell cycles is regional and direct.

Gli3 is required in Emx1+ progenitors for the development of the corpus callosum.

The corpus callosum (CC) is the largest commissure in the forebrain and mediates the transfer of sensory, motor and cognitive information between the cerebral hemispheres. During CC development, a number of strategically located glial and neuronal guidepost structures serve to guide callosal axons across the midline at the corticoseptal boundary (CSB). Correct positioning of these guideposts requires the Gli3 gene, mutations of which result in callosal defects in humans and mice. However, as Gli3 is widely expressed during critical stages of forebrain development, the precise temporal and spatial requirements for Gli3 function in callosal development remain unclear. Here, we used a conditional mouse mutant approach to inactivate Gli3 in specific regions of the developing telencephalon in order to delineate the domain(s) in which Gli3 is required for normal development of the corpus callosum. Inactivation of Gli3 in the septum or in the medial ganglionic eminence had no effect on CC formation, however Gli3 inactivation in the developing cerebral cortex led to the formation of a severely hypoplastic CC at E18.5 due to a severe disorganization of midline guideposts. Glial wedge cells translocate prematurely and Slit1/2 are ectopically expressed in the septum. These changes coincide with altered Fgf and Wnt/ß-catenin signalling during CSB formation. Collectively, these data demonstrate a crucial role for Gli3 in cortical progenitors to control CC formation and indicate how defects in CSB formation affect the positioning of callosal guidepost cells.

Povidone-iodine contact time and lid speculum use during intravitreal injection.

PURPOSE: To determine the time necessary for 5% povidone-iodine (PI) to cause a significant reduction in colony-forming units and whether a lid speculum increases the conjunctival flora. METHODS: This was a prospective randomized study of 131 eyes undergoing intravitreal injection. Conjunctival samples were collected in a prospective protocol at three points before intravitreal injection: (1) no intervention (baseline), (2) after placement of a lid speculum, and (3) after treatment with 5% PI. Participants were randomized into three different PI exposure intervals. Cultures were incubated for 6 days, and the resulting colony-forming units were tallied for each intervention. RESULTS: Use of 5% PI caused significant decrease in the number of colony-forming units (P < 0.0001). Exposure to PI for 15 seconds did not cause a significant reduction in conjunctival bacteria (P = 0.08), but a significant reduction was observed after 30 seconds of exposure and beyond (P = 0.0003). Placement of a lid speculum did not result in a significant increase or decrease in the number of colony-forming units when compared with baseline (P = 0.47). CONCLUSION: The use of 5% PI causes a significant reduction in bacterial colonies, and 30 seconds of exposure appears to be an adequate time to decrease conjunctival bacterial counts. Lid speculum use before intravitreal injection does not affect the overall conjunctival flora.

Activation of Wnt/ß-catenin signalling affects differentiation of cells arising from the cerebellar ventricular zone.

Development of the cerebellum proceeds under the precise spatio-temporal control of several key developmental signalling pathways, including the Wnt/ß-catenin pathway. We recently reported the activity of Wnt/ß-catenin signalling in the perinatal cerebellar ventricular zone (VZ), a germinal centre in the developing cerebellum that gives rise to GABAergic and glial cells. In order to investigate the normal function of Wnt/ß-catenin signalling in the VZ and the cell lineages it gives rise to, we used a combination of ex vivo cerebellar slice culture and in vivo genetic manipulation to dysregulate its activity during late embryonic development. Activation of the pathway at the cerebellar ventricular zone led to a reduction in the number of cells expressing the glial lineage markers Sox9 and GFAP and the interneuron marker Pax2, but had no consistent effect on either proliferation or apoptosis. Our findings suggest that activation of the Wnt/ß-catenin pathway in the cerebellar ventricular zone causes a shift in the cell types produced, most likely due to disruption of normal differentiation. Thus, we propose that regulation of Wnt/ß-catenin signalling levels are required for normal development of cells arising from the cerebellar ventricular zone during late embryogenesis.