Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway

<p>Abstract</p> <p>Background</p> <p>Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K⁺channels.</p> <p>Case presentation</p> <p>Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the <it>vegf-a, flt-1, kdr</it>, and <it>hif1-α </it>transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K⁺channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.</p> <p>Conclusions</p> <p>We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the <it>vegf-a</it>, <it>flt-1</it>, <it>kdr </it>and <it>hif1-α </it>transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the <it>herg1 </it>gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A.</p

Topical ciclosporin in the treatment of ocular surface disorders

Mounting evidence suggests that inflammation is the key factor in the pathogenesis of various ocular surface diseases, with a complex interplay of genetic, environmental, and psychosocial factors. Management of these conditions is often challenging. Topical corticosteroids, with their associated side effects, are the mainstay of current treatments for patients with vision threatening disease. Ciclosporin A is an immunomodulator that specifically inhibits T lymphocyte proliferation. Recently, a topical ciclosporin preparation was approved by the US Food and Drug Administration and became available for use in ophthalmology. Given the increasing use of ciclosporin eye drops, the goal of this article is to provide the reader with an overview of the well established uses of ciclosporin and to help refine the questions that should be addressed by future investigations

hemorrhage and preretinal membrane in Valsalva retinopathy

Case report: Optical coherence tomography features of a sub-internal limiting membrane (ILM) premacular hemorrhage and dome-shaped preretinal membrane secondary to Valsalva retinopathy are described.Comments: The origin of the membrane (internal limiting membrane or posterior hyaloid) and the location of the blood (sub-ILM, or subhyaloid) are difficult to define by ophthalmoscopy

Trochlear nerve palsy in herpes zoster opthalmicus

Herpes zoster ophthalmicus (HZO) causes a wide range of ocular manifestations, and ophthalmoplegia is among the infrequent complications. The most commonly affected nerve is the third nerve, the least affected is the trochlear nerve. Herein, we describe two cases of isolated fourth nerve palsy associated with HZO. In both cases, the onset of ophthalmoplegia was shortly after the appearance of skin lesions, and both of the patients received oral acyclovir. Complete recovery was observed in a period of a few months

Hyperhomocysteinemia: a risk factor for retinal vein occlusion.

PURPOSE: The aim of the study was to investigate the plasma homocysteine levels in patients with retinal vein occlusion (RVO) in order to reveal whether hyperhomocysteinemia was a risk factor for RVO. METHODS: Thirty-three consecutive patients diagnosed to have RVO of any type and 25 age- and sex-matched controls without RVO were included in this prospective case-control study. Data regarding age, sex, history of hypertension, diabetes mellitus, other vascular events, glaucoma, medications and smoking habits were obtained from all subjects. Several laboratory tests relating to vascular disease including cholesterol, triglyceride and hematocrit were checked. The plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography (normal range: 5-15 micromol/l). Plasma folate, vitamin B(12) and creatinine levels were also studied since these vitamins and impairment of renal function might affect plasma tHcy values. RESULTS: Patients with RVO had a significantly higher tHcy level (median: 11.7 micromol/l, range: 7.2-25 micromol/l) compared to controls (median: 10.3 micromol/l, range: 6.7-13.4 micromol/l; p = 0.005). Nine of 33 patients with RVO (27.3%) had an elevated plasma tHcy level, whereas none of the controls had an abnormal tHcy value (p = 0.004). Plasma folate, vitamin B(12) and creatinine levels were comparable between the two groups (p > 0.05). CONCLUSIONS: The present study suggests an association between hyperhomocysteinemia and RVO. Further controlled studies with a large number of cases are needed to investigate the exact role of hyperhomocysteinemia in RVO

age-related macular degeneration

Aim: To assess the intraobserver repeatability of automated versus adjusted optical coherence tomography ( OCT) measurements in patients with neovascular age- related macular degeneration ( NVAMD). Methods: Ten eyes with NVAMD from 10 consecutive patients underwent two OCT measurements within 5 days by a single operator. Automated and adjusted central 1- mm foveal thickness and automated and adjusted total macular volume were measured in each study eye. The term 'adjusted' refers to manually corrected values, in which the interface landmarks for measurements are selected by the operator using Stratus (R) scan profiling and custom software. Bland- Altman method and bootstrap comparison of intraclass correlations ( ICCs) were used for repeatability analysis. Results: Bland- Altman comparison did not reveal any statistically significant difference in any parameter, when results at first and second examination were compared ( p > 0.05), indicating that the repeated measurements are similar. Further analysis was conducted using the bootstrap comparison of ICCs. The difference between adjusted and automated foveal thickness ICCs ( r = 0.945 and 0.635, respectively) was significant ( p = 0.031), indicating higher repeatability for adjusted foveal thickness. The ICCs for adjusted and automated total macular volume ( r = 0.873 and 0.863, respectively) showed no statistically significant difference ( p = 0.881). Conclusion: The repeatability of adjusted retinal thickness measurements, in which the errors of retinal boundary detection by OCT analysis software is corrected by the operator using scan profiling, is found to be higher than that of automated ones in this small group of NVAMD patients when performed by a single experienced operator. Copyright (c) 2006 S. Karger AG, Basel

Efficacy and safety of rimexolone 1% versus prednisolone acetate 1% in the control of postoperative inflammation following phacoemulsification cataract surgery.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of rimexolone 1% ophthalmic suspension compared to that of 1% prednisolone acetate in the control of inflammation in eyes undergoing cataract extraction with phacoemulsification followed by posterior chamber intraocular lens implantation. METHODS: Forty-eight patients who underwent uncomplicated cataract extraction with phacoemulsification followed by posterior chamber IOL implantation constituted the study group of this prospective, randomized, double-masked investigation. Patients were randomly assigned to two treatment groups; rimexolone 1% ophthalmic suspension (27 subjects) or prednisolone acetate 1% (21 subjects). Postoperatively, patients used topical rimexolone or prednisolone drops four times a day for 15 days. Patients were examined at the first postoperative day (day 1), and days 3, 7 and 15. The major efficacy parameters assessed clinically on each visit were anterior chamber cells, anterior chamber flare and conjunctival hyperemia. Safety of the rimexolone was evaluated by IOP values and the presence of adverse effects. RESULTS: Regarding all three efficacy parameters, rimexolone was found to be clinically and statistically equivalent to prednisolone acetate. Intraocular pressure values during the postoperative period were also similar in both groups. CONCLUSION: Rimexolone 1% ophthalmic suspension is both an effective and safe topical steroid in controlling postoperative inflammation after cataract extraction with phacoemulsification

Subjective visual experience and pain level during phacoemulsification and intraocular lens implantation under topical anesthesia.

PURPOSE: To investigate the subjective visual experiences and pain during the phacoemulsification and intraocular lens (IOL) implantation under topical anesthesia, and whether these parameters change according to the stage of phacoemulsification cataract surgery. METHODS: Forty eyes of 40 patients with cataract undergoing phacoemulsification and IOL implantation under topical anesthesia were included in this study. The patients were told that they would be asked about their visual experiences and pain level, if any, during every stage of the surgery. As for degree of the pain, a 5-grade scale was used. The surgery was divided into 9 stages, i.e., clear corneal incision, continuous curvilinear capsulorhexis, side-port incisions at 3 and 9 o'clock positions, hydrodissection, nuclear rotation, phacoemulsification, bimanual irrigation and aspiration, IOL implantation, apposition of corneal incisions with stromal hydration. RESULTS: All subjects (100%) reported that they had seen some kind of light during the operation. Thirty-eight patients (95%) said that they had seen one or more colors. In 32 patients (80%), the light intensity decreased, and colors blurred significantly following the hydrodissection. As for the pain level during surgery, the overall pain score was found to be 0.40. The highest mean pain score was noted during IOL implantation stage followed by phacoemulsification and bimanual irrigation-aspiration. CONCLUSION: Topical anesthesia is both a safe and effective method for small-incision clear corneal phacoemulsification cataract surgery. Patients may experience visual sensations, and the pain felt during the operation is low and tolerable. Visual experiences and pain level may change according to the stage of phacoemulsification cataract surgery