Summary Adipose tissue–derived “stem cells” have been increasingly used by “stem-cell clinics” in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue–derived “stem cells” at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients’ visual acuity ranged from 20/200 to no light perception.

BackgroundGlycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2’s roles beyond embryonic neurogenesis have yet to be defined.MethodUsing a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 −/− mouse for evidence of degenerative neuropathology. A conditional deletion of Gde2 was used to study the temporal requirements for GDE2 in neuronal survival. Biochemical approaches identified deficits in the processing of GPI-anchored GDE2 substrates in the SOD1 G93A mouse model of familial Amyotrophic Lateral Sclerosis that shows robust motor neuron degeneration.ResultsHere we show that GDE2 expression continues postnatally, and adult mice lacking GDE2 exhibit a slow, progressive neuronal degeneration with pathologies similar to human neurodegenerative disease. Early phenotypes include vacuolization, microgliosis, cytoskeletal accumulation, and lipofuscin deposition followed by astrogliosis and cell death. Remaining motor neurons exhibit peripheral motor unit restructuring causing behavioral motor deficits. Genetic ablation of GDE2 after embryonic neurogenesis is complete still elicits degenerative pathology, signifying that GDE2’s requirement for neuronal survival is distinct from its involvement in neuronal differentiation. Unbiased screens identify impaired processing of Glypican 4 and 6 in Gde2 null animals, and Glypican release is markedly reduced in SOD1 G93A mice.ConclusionsThis study identifies a novel function for GDE2 in neuronal survival and implicates deregulated GPI-anchored protein activity in pathways mediating neurodegeneration. These findings provide new molecular insight for neuropathologies found in multiple disease settings, and raise the possibility of GDE2 hypofunctionality as a component of neurodegenerative disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-017-0148-1) contains supplementary material, which is available to authorized users.

PurposeThe purpose of this study was to report clinical features and outcomes in patients with giant retinal tears (GRTs) undergoing vitreoretinal surgery and to compare data from this contemporary series to a previous study from the same institution.Materials and methodsA retrospective, interventional, consecutive case series was conducted for all patients diagnosed with GRTs who underwent vitreoretinal surgery between January 2011 and August 2017. Intraoperative data including the use of scleral buckling, perfluorocarbon liquid, and intraocular tamponade were collected and compared according to GRT size. These parameters, along with postoperative anatomic success and best-corrected visual acuity (BCVA), were compared with the previous series.ResultsThe study included 80 eyes of 79 patients with a presentation of retinal detachment with a GRT. Management approach for repair of GRT-associated retinal detachments included scleral buckle (SB) alone (three eyes, 4%), pars plana vitrectomy (PPV) (16 eyes, 20%), and combined SB/PPV (61 eyes, 76%). Perfluorocarbon liquids were used in 60/77 eyes (78%) undergoing PPV, and silicone oil was used in 54/77 eyes (70%). Single surgery success rate was in 69/80 eyes (86%). Eyes managed with SB (including SB alone and SB/PPV) or PPV without SB had similar rates of recurrent retinal detachment (16% vs 6%; P=0.33). Anatomic success was achieved in 76/80 eyes (95%) with one or more surgical procedures, and 54/80 eyes (68%) achieved postoperative BCVA of ≥20/400.ConclusionsIn the current series, repairs of retinal detachment due to GRTs were most commonly managed with combined PPV/SB and perfluorocarbon liquid, resulting in reasonably generally favorable anatomic and visual outcomes.

The mammalian cortex is a multilaminar structure consisting of specialized layer-specific neurons that form complex circuits throughout the brain and spinal cord. These neurons are generated in a defined sequence dictated by their birthdate such that early-born neurons settle in deep cortical layers whereas late-born neurons populate more superficial layers. Cortical neuronal birthdate is partly controlled by an intrinsic clock-type mechanism; however, the role of extrinsic factors in the temporal control of cell-cycle exit is less clear. Here, we show that Gde2, a six-transmembrane protein that induces spinal neuronal differentiation, is expressed in the developing cortex throughout cortical neurogenesis. In the absence of Gde2, cortical progenitors fail to exit the cell cycle on time, remain cycling, accumulate and exit the cell cycle en masse towards the end of the neurogenic period. These dynamic changes in cell-cycle progression cause deficits and delays in deep-layer neuronal differentiation and robust increases in superficial neuronal numbers. Gde2−/− cortices show elevated levels of Notch signaling coincident with when progenitors fail to differentiate, suggesting that abnormal Notch activation retains cells in a proliferative phase that biases them to superficial fates. However, no change in Notch signaling is observed at the time of increased cell-cycle exit. These observations define a key role for Gde2 in controlling cortical neuronal fates by regulating the timing of neurogenesis, and show that loss of Gde2 uncovers additional mechanisms that trigger remaining neuronal progenitors to differentiate at the end of the neurogenic period.

Purpose: To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. Methods: This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. Results: Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). Conclusion: Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

Purpose To evaluate whether high resolution optical coherence tomography (HR-OCT) can aid in the differentiation of inflammatory versus non-inflammatory causes of peripheral corneal thinning. Methods Retrospective chart review of ten patients with peripheral corneal thinning and their respective slit lamp photographs and HR-OCT images. Results Ten patients were identified who had peripheral corneal thinning and HR-OCT images. Five had a clinical history consistent with Terrien's marginal degeneration (TMD) while five had thinning thought to be inflammatory in origin. In the eyes with presumed TMD, patients denied pain or inflammation. HR-OCT images demonstrated stromal thinning in the presence of an intact epithelium. The stroma underneath the epithelium in the area of thinning had a similar reflectivity pattern as the non-affected cornea. There was epithelial marsupialization evident in 2 of the 5 images. In the 4 patients with a clinical history of prior inflammation (bulbar hyperemia, pain), and in the one patient with active inflammation at the time of HR-OCT imaging, HR-OCT also demonstrated thinning with an intact epithelium. In contrast to the TMD group, in the group with signs of inflammation, a dense hyper-reflective band was noted in the stroma directly below the epithelium in the area of thinning, suggestive of scarring and/or cellular infiltration. Conclusion In patients with a clinical history of inflammation and corneal thinning, HR-OCT revealed a hyper-reflective band directly under the epithelium in the area of thinning which was not seen in patients with presumed non-inflammatory melts and thinning.

This case demonstrates the complexity of FK management and introduces autologous serum tears as a viable management option when conservative approaches to this condition fail.

Background/aimsVitrectomy to repair retinal detachment is often performed with either non-contact wide-angle viewing systems or wide-angle contact viewing systems. The purpose of this study is to assess whether the viewing system used is associated with any differences in surgical outcomes of vitrectomy for primary non-complex retinal detachment repair.MethodsThis is a multicenter, interventional, retrospective, comparative study. Eyes that underwent non-complex primary retinal detachment repair by either pars plana vitrectomy (PPV) alone or in combination with scleral buckle/PPV in 2015 were evaluated. The viewing system at the time of the retinal detachment repair was identified and preoperative patient characteristics, intraoperative findings and postoperative outcomes were recorded.ResultsA total of 2256 eyes were included in our analysis. Of those, 1893 surgeries used a non-contact viewing system, while 363 used a contact lens system. There was no statistically significant difference in single surgery anatomic success at 3 months (p=0.72), or final anatomic success (p=0.40). Average postoperative visual acuity for the contact-based cases was logMAR 0.345 (20/44 Snellen equivalent) compared with 0.475 (20/60 Snellen equivalent) for non-contact (p=0.001). After controlling for numerous confounding variables in multivariable analysis, viewing system choice was no longer statistically significant (p=0.097).ConclusionThere was no statistically significant difference in anatomic success achieved for primary retinal detachment repair when comparing non-contact viewing systems to contact lens systems. Postoperative visual acuity was better in the contact-based group but this was not statistically significant when confounding factors were controlled for.