Unifocality as Prognostic Factor for Unilateral Retinoblastoma: Preliminary Results of 32 Eyes Treated with Intra-Arterial Chemotherapy Alone

Purpose: To evaluate the role of intra-arterial chemotherapy (IAC) in the management of unilateral, unifocal retinoblastoma (RB) as a single therapy, associated to neither focal nor systemic adjunctive therapies. Methods: Prospective, single center, interventional case series of 32 consecutive eyes diagnosed with unilateral unifocal RB and treated exclusively with selective ophthalmic intra-arterial chemotherapy, with no adjunctive systemic or focal treatments. Results: Full regression of the lesion was observed in 30 eyes (93.75%). 2 eyes were enucleated. Ophthalmoscopic remissions type I and III with higher calcific component were achieved. Additionally, neither recurrences nor new tumors appeared during the patient follow-up, which ranged from 10 months to 13 years. Conclusion: Selective intra-arterial chemotherapy has demonstrated to be highly effective in terms of disease control and anatomical preservation in case of unilateral unifocal disease, without requiring any additional systemic and/or focal therapy

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age

Dual effect of morphine in long-term social memory in rat

Background and Purpose Bimodal dose-response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (μg) and high (mg, analgesic) doses, changed the learning process. Experimental Approach In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re-exposed to each other, in the absence of morphine. Key Results Low doses of morphine, comparable with endogenous brain concentrations, enhanced long-term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through μ-opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses. Conclusions and Implications Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs

Spinal administration of mGluR5 antagonist prevents the onset of bortezomib induced neuropathic pain in rat

Peripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co-administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy

Management of intraocular pressure elevation during hemodialysis of neovascular glaucoma: A case report

Background: It is generally accepted that dialysis may lower plasma osmolality at a faster rate than changes in ocular osmolality. This osmotic difference causes water to migrate from the plasma into the aqueous humor, increasing intraocular pressure. Certain authors have described IOP increase in patients with narrow angles. Case presentation: Here we report a neovascular glaucoma patient who experienced a substantial increase in IOP associated with severe eye pain and blurred vision during sessions of dialysis. The patient had been refractory to several antiglaucoma drugs and improved after intravenous administration of 20 % hyperosmotic glucose solution with dialysis and pan-retinal photocoagulation. Conclusion: It is the first report in which intravenous glucose administration and reduction of neovascularization by argon laser pan-retinal photocoagulation successfully managed IOP increase during dialysis in neovascular glaucoma. Further clinical studies are required to confirm our results

Prophylactic role of acetyl-l-carnitine on knee lesions and associated pain in a rat model of osteoarthritis.

Aims: in the present study, our aim was to validate in vivo the prophylactic role of acetyl-l-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death. Main methods: animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC. Key findings: morphological analysis of knee-joint from MIA and ALC co-treated rats showed that the total pathological score attributed to histological findings was dramatically lower in rats treated with MIA in the presence of ALC. OA chondrocyte overexpression of pathogenic collagenase matrix-metallopeptidase-13 (MMP13) could be decreased in knee-cartilage from MIA/ALC rats; whereas type II collagen (COL2) expression level could be partially increased to control value. ALC twice daily treatment was able to attenuate pain in OA rat knee as revealed by mechanical behavioral tests. Significance: in our experiments, pain that is usually associated with OA, was correlated with the severity of histopathological findings. Our findings show that there is a place for ALC as chondroprotective agents in cartilage degradation and strongly support the prophylactic and therapeutic potentials of ALC in knee-OA patients

Natural history of an early diagnosed retinocytoma: case report and literature review

Purpose To study the ophtahlmoscopic evolution of a retinocytoma diagnosed in a 8 months old boy. Methods The patient was referred at the Referral Center for Retinoblastoma of the University of Siena, with the suspect of unilateral retinoblastoma. The boy was diagnosed as having retinocytoma based on ophthalmoscopic appearance. Monthly ophthalmoscopic and ecographic evaluation were recommended. Detailed fundus drawings and fundus photographs and descriptions of the retinocytoma were collected. The little boy underwent also MRI, genetic testing and fluorangiography. Results Throughout the months, we observed a tumor regression from avascular mass with fish‐flesh appearance and microscopic calcifications to a retinal transparent mass with calcifications, retinal cysts and surrounded by chorioretinal atrophy. Conclusion Retinocytoma is a rare benign retinal tumor with characteristic clinical features. Usually diagnosed in parents of retinoblastoma children, “silent” retinocytoma diagnosis is more rare in babies. In our case, we observed a natural “regression” of a retinocytoma in a 8 months old boy kept under close RETCAM follow‐up for the risk of malignant transformation

Superselective intra-arterial chemotherapy complications in advanced retinoblastoma

Purpose The purpose of this study is to report the complications of superselective intra-arterial chemotherapy with melphalan in children undergoing treatment for advanced intraocular retinoblastoma. Methods 49 eyes of 43 children with advanced intraocular retinoblastoma (Reese-Ellsworth Group Vb or International Classification Group D) were treated with superselective intra-ophthalmic artery infusion of melphalan. 22 eyes of 43 children were first diagnosis. 27 eyes of 43 children had previously failed traditional management with systemic chemotherapy and focal therapies and underwent intra-ophthalmic artery infusion of melphalan as an alternative option to enucleation. Serial complications RETCAM images were collected. Results Ophthalmic artery cannulation was successfully performed in 49 eyes of 43 patients. 9 eyes out of 43 (20.9%) patients were enucleated. 4 eyes out of 43 (9.3%) patients were lost to follow-up. No severe systemic side effects occurred. Grade III neutropenia was seen in 3 patients (0.6%). No transfusions were required. 25 (58.1%) patients developed eyelid hyperaemia, 10 (23.2%) frontal region skin rash, 12 (27.9%) emiptosis, 6 (13.9%) eyelid edema, 2 (4.6%) frontal alopecia, 2 (4.6%) eyelashes loss, 2 (4.6%) chorioretinal atrophy, 1 (2.3%) acute ischemic optic neuropathy, all resolved spontaneously. 1 case (2.3%) with permanent ptosis underwent surgery. 1 case (2.3%) presented Roth’s spots. Conclusion Ophthalmic intra-arterial infusion with melphalan is a promising globe-conserving treatment option in advanced retinoblastoma cases with minimal systemic side effects

CNS abnormalities in retinoblastoma patients

Purpose The presence of CNS abnormalities on MR images in a large group of consecutive patients with retinoblastoma (RTB) is evaluated. Mental retardation and congenital brain anomalies are reported in patients with RTB, mostly in combination with 13q deletion syndrome. Pineoblastoma (PNB) is the most important and “life threatening” condition associated with hereditary RTB, but recent studies suggest an association with pineal cysts. This association is important because some PNB mimic pineal cysts Methods CNS MR images of 320 consecutive patients with RTB from 2000 to 2010 were evaluated by neuroradiologists for tumors, structural anomalies, myelinization, and coincidental findings. Clinical records were reviewed for laterality, heredity, and the presence of the 13q deletion syndrome. Results The hereditary group (patients with bilateral and unilateral proved RB1-germline mutation) included 42 (48.2%) of 87 patients. Nine patients had 13q deletion syndrome. Normal findings on brain MR images were seen in 305 (95.3%) patients. One PNB was detected in a patient with hereditary RTB and 2 arachnoid cysts in 2 sporadic unilateral RTB patients; one cerebral and corpus callosum atrophy and 3 pineal cysts were also detected (2 non hereditary, 1 in 13q deletion syndrome). Corpus callosum agenesis was found in 3 patients (two in 13q deletion syndrome, 1 in hereditary RTB) and corpus callosum hypoplasia in 6 patients (2 twins, 4 sporadic RTB, 1 familial RTB). Chiari I syndrome was found in two cases Conclusion PNB is associated with hereditary RTB, and structural brain abnormalities are associated not only with 13q deletion syndrome. Pineal cysts can be detected in patients with sporadic RTB and/or with 13q deletion syndrome