Corneoscleral involvement in Crohn's disease. Discussion of a case

The authors are reporting an unusual case of scleral involvement in a case of Crohn's disease. A distinctive subepithelial keratopathy developed which though uncommon, should be regarded as a distinct clinical sign of Crohn's disease. The exact situation of ocular lesions among extra-intestinal complications of Crohn's disease, their incidence and aspects are discussed. The possible immunological basis of these manifestations, still unconvincing, is exposed and related to local deposition of antigen-antibody complexes.     

Poisoning of retinal pigment epithelium by deferoxamine. A case report

A patient undergoing hemodialysis was treated intravenously with desferrioxamine (3 g) for an aluminum encephalopathy. He presented a sudden xanthopsia with visual loss. Fundus examination showed diffuse macular irregular pigmentary disturbances. We discuss current knowledge and possible pathogenesis of these observations published since 1983. Awareness of the side effects of desferrioxamine implies an ophthalmologic follow up similar as chloroquine.     

Association of intermediate uveitis with HLA-A28: definition of a new systemic syndrome?

Background: Endogenous posterior uveitis (PU) can be associated with systemic diseases, and certain forms have strong association with HLA antigens. Much less is known regarding intermediate uveitis (IU). The purpose of this study was to determine whether IU is associated with the HLA system and whether it can be associated with systemic symptoms.Methods: In 179 consecutive patients consulting for uveitis, a detailed history was obtained and a physical examination performed. HLA typing for 71 HLAA, B, DR and DQ antigens, laboratory tests, and radiography of the chest, sinuses, and sacroiliac joints were systematically performed.Results: Thirty-two patients (18%) had IU; 51 (28.5%) had PU and constituted our internal control group. Nine of the patients with IU (28%) had the HLA-A28 antigen, compared with 8.1 % of a healthy control population and 8.6% of the patients with PU (P < 0.001). An associated disease was found in four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P<0.05 and P<0.01 respectively); 55% had gonalgias and hypocomplementemia compared with 9% and 2% respectively (P < 0.01 and P < 0.001).Conclusions: IU is significantly associated with HLA-A28; patients having this antigen may represent a subset of the disease characterized by an increased prevalence of arthralgias and hypocomplementemia.     

Effect of autologous platelet concentrate in surgery for idiopathic macular hole: results of a multicenter, double-masked, randomized trial. Platelets in Macular Hole Surgery Group.

OBJECTIVE: To evaluate prospectively the efficacy and safety of autologous platelet concentrate (APC) as an adjuvant in surgery for idiopathic macular hole. DESIGN: Multicenter, double-masked, randomized clinical trial. SETTING: Four university-based ophthalmology clinics. PARTICIPANTS: One hundred ten patients with stage 3 or 4 idiopathic full-thickness macular holes of less than 3 years' duration were randomized (53 eyes to the platelet group and 57 eyes to the control group). INTERVENTIONS: Standardized macular hole surgery versus surgery combined with injection of an APC. In all cases, the procedure consisted of three-port pars plana vitrectomy, posterior hyaloid separation, and nonexpansile fluid-gas exchange. After the fluid-gas exchange, patients were randomized to receive either injection of an APC or no adjunctive treatment. After surgery, patients were positioned face down for 12 days. Platelet counts showed that the concentrates contained a mean of 96.106 platelets (range, 82-102). MAIN OUTCOME MEASURES: Anatomic and functional evaluations were performed at 1, 3, and 6 months after surgery in a double-masked fashion by an independent observer. The main outcome was reapposition of the edge of the macular hole 1 month after surgery. Secondary outcomes were anatomic status at 3 and 6 months, changes in Early Treatment Diabetic Retinopathy Study score, and complications. RESULTS: One month after surgery, the anatomic success rate in the platelet group was 52 of 53 (98%; 95% confidence interval, 0.90-1.00) versus 47 of 57 (82%; 95% confidence interval, 0.70-0.91) in the control group (P = 0.009, Fisher's exact test; relative risk, 0.11; 95% confidence interval, 0.01-0.81). Visual acuity was not significantly different between the two groups at any timepoint. There were no complications specifically attributable to the platelet injection. CONCLUSION: Injection of APC improved significantly the anatomic success rate of surgery for idiopathic macular holes of less than 3 years' duration, but postoperative visual acuity of the platelet group was not statistically different from the control group.     

Central retinal vein occlusion and opto-ciliary shunts. An angiographic diagnosis]

Opto-ciliary shunts are compensatory bypass channels from the retinal venous system to the choroidal veins in case of long standing central retinal vein occlusion. Indocyanine green angiography with the Scanning Laser Ophtalmoscope may be helpful to differentiate acquired optociliary shunts from retinal or choroidal arteriovenous malformations.     

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium

Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease.Irreversible blindness caused by retinal diseases, such as inherited retinopathies, age-related macular degeneration (AMD), or glaucoma, is mainly due to the impairment or loss of function of photoreceptor cells, supporting retinal pigmented epithelium (RPE) or retinal ganglion cells (RGCs). Rescuing the degenerated retina is a major challenge for which specific cell replacement is one of the most promising approaches (1, 2). Pluripotent stem cells, like human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs), have the ability to be expanded indefinitely in culture and could be used as an unlimited source of retinal cells for the treatment of retinal degenerative diseases (3, 4). Several publications have indicated that hESCs and hiPSCs can be differentiated into RPE cells spontaneously after fibroblast growth factor (FGF) 2 removal (5–7) or by different floating aggregate methods (8–11). Concerning neural retinal cells, a growing body of convergent data has demonstrated the ability of hESCs or hiPSCs to be committed into the neural retinal lineage and further differentiated into cells expressing photoreceptor markers (12–15). Recent innovative approaches using 3D cultures from embryoid bodies (EBs) of hESCs or hiPSCs allowed the self-formation of optic cup (OC) structures (16) or the generation of optic vesicle (OV)-like structures (17), depending on the addition of exogenous molecules and different substrates used. These protocols require multiple steps and trained handling, which are not always compatible with the manufacturing process for therapeutic approach or drug screening that need a large-scale production of cells of interest. Therefore, very simple and reliable approaches minimizing the use of exogenous molecules should be developed to generate hESCs or hiPSC-derived retinal cells.In the present study, we report a new retinal differentiation process using confluent hiPSCs, without cell clumps or EB formation and in the absence of Matrigel or serum. We demonstrate that integration-free hiPSCs derived from adult human dermal fibroblasts (AHDFs) cultured in proneural medium can simultaneously generate RPE cells and self-forming neural retinal (NR)-like structures within 2 wk and that, when switched to floating cultures, structures containing retinal progenitor cells (RPCs) can differentiate into all retinal cell types, including RGCs and precursors of photoreceptors, needed for therapeutic applications.     

Neuroglobin Gene Therapy Prevents Optic Atrophy and Preserves Durably Visual Function in Harlequin Mice

Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates the adverse effects of hypoxic and ischemic insults. We previously demonstrated the functional link between NGB and mitochondria since it is required for respiratory chain function. Thus, here, we evaluated the relevance of this effect in the Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss and optic atrophy due to a respiratory chain complex I (CI) defect. A twofold decrease of NGB amounts was observed in Hq retinas. We constructed a recombinant adeno-associated virus which combines to the mouse NGB open reading frame, its 5′ and 3′UTR, for guarantying mRNA stability and translation capacity. The vector was administrated intravitreally to Hq mice and NGB expression was stable for up to 7 months without negative effect on retinal architecture or function. On the contrary, RGCs and their axons were substantially preserved from degeneration; consequently, CI activity in optic nerves was protected conferring improvements in vision. Hence, we established that NGB prevents respiratory chain impairment, therefore, protecting visual function otherwise compromised by mitochondrial energetic failure.     

Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis

Chronic calcifying pancreatitis is characterized by the formation of intraductal protein plugs or precipitates and calcified stones in ducts. Similar precipitates may be collected by endoscopic retrograde catheterization of the main pancreatic duct. They are present in the pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis. Protein analysis of these precipitates was performed to try to elucidate the mechanism of stone formation. Two protein fraction were separated by extraction of precipitates. One fraction was easily soluble in saline and contained a small amount of most of the proteins of pancreatic juice. The other fraction was soluble in citrate or ethylenediaminetetraacetate and contained a few proteins with close isoelectric points and identical molecular weight (13,500). These proteins showed immunological identity with the "stone protein" isolated from human pancreatic calculi. Our data demonstrate that the major citrate-soluble protein of precipitates in pancreatic juice is identical with "stone protein". They are strongly support the concept that this protein is the organic matrix of pancreatic stones. Different mechanisms are proposed to explain the phenomenon of protein precipitation that frequently occurs in alcoholic subjects and patients with chronic calcifying pancreatitis.