Bilateral Sequential NAION: A Comparison of Visual Outcomes in Fellow Eyes Using Quantitative Analysis of Goldmann Visual Fields

Purpose: Previous studies of the visual outcome in bilateral non-arteritic anterior ischemic optic neuropathy (NAION) have yielded conflicting results, specifically regarding congruity between fellow eyes. Prior studies have used measures of acuity and computerized perimetry but none has compared Goldmann visual field outcomes between fellow eyes. In order to better define the concordance of visual loss in this condition, we reviewed our cases of bilateral sequential NAION, including measures of visual acuity, pupillary function and both pattern and severity of visual field loss.Methods: We performed a retrospective chart review of 102 patients with a diagnosis of bilateral sequential NAION. Of the 102 patients, 86 were included in the study for analysis of final visual outcome between the affected eyes. Visual function was assessed using visual acuity, Goldmann visual fields, color vision and RAPD. A quantitative total visual field score and score per quadrant was analyzed for each eye using the numerical Goldmann visual field scoring method previously described by Esterman and colleagues. Based upon these scores, we calculated the total deviation and pattern deviation between fellow eyes and between eyes of different patients. Statistical significance was determined using nonparametric tests.Results: A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P = 0.0101), global visual field (P = 0.0001), superior visual field (P = 0.0001), and inferior visual field (P = 0.0001). In addition, the mean deviation of both total (P = 0.0000000007) and pattern (P = 0.000000004) deviation analyses was significantly less between fellow eyes ("intra"-eyes) than between eyes of different patients ("inter"-eyes).Conclusions: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION. These findings may also be useful for evaluating efficacy of therapeutic interventions.

Chemotherapy for retinoblastoma.

Retinoblastoma is the most common eye cancer in children. Pilot studies of chemotherapy for intraocular retinoblastoma have been reported by several groups, using different combinations, dosages, schedules, and durations of carboplatin, etoposide, or teniposide, with or without vincristine, and with or without cyclosporine to counteract multidrug resistance. All studies of chemotherapy for intraocular retinoblastoma have included consolidation by focal therapy, with or without radiation. Chemotherapy alone reduces tumor size but does not cure retinoblastoma. Focal therapy, consisting of photocoagulation, thermotherapy, cryotherapy, or brachytherapy, is necessary to consolidate chemotherapy response.

Assessing the Functionality and Biocompatibility of a Wireless Contact Lens Sensor for 24 hour-intraocular Pressure Monitoring in Volunteers: Preliminary Results

Purpose: In vitro studies in porcine eyes have demonstrated a good correlation between induced intraocular pressure variations and corneal curvature changes, using a contact lens with an embedded microfabricated strain gauge. Continuous 24 hour-intraocular pressure (IOP) monitoring to detect large diurnal fluctuation is currently an unmet clinical need. The aims of this study is to evaluate precision of signal transmission and biocompatibility of 24 hour contact lens sensor wear (SENSIMED Triggerfish®) in humans. Methods: After full eye examination in 10 healthy volunteers, a 8.7 mm radius contact lens sensor and an orbital bandage containing a loop antenna were applied and connected to a portable recorder. Best corrected visual acuity and position, lubrication status and mobility of the sensor were assessed after 5 and 30 minutes, 4, 7 and 24 hours. Subjective comfort was scored and activities documented in a logbook. After sensor removal full eye examination was repeated, and the registration signal studied. Results: The comfort score was high and did not fluctuate significantly, except at the 7 hour-visit. The mobility of the contact lens was minimal but its lubrication remained good. Best corrected visual acuity was significantly reduced during the sensor wear and immediately after its removal. Three patients developed mild corneal staining. In all but one participant we obtained a registration IOP curve with visible ocular pulse amplitude. Conclusions: This 24 hour-trial confirmed the functionality and biocompatibility of SENSIMED Triggerfish® wireless contact lens sensor for IOP-fluctuation monitoring in volunteers. Further studies with a range of different contact lens sensor radii are indicated.

Expression of Chemokine Receptors in Uveal Melanoma

Purpose:Chemokine receptors are transmembrane G coupled proteins that might be involved in the directional metastatic migration of tumor cells to specific organs. CXCR4 and CCR7 have been implicated in the selective metastasis of cutaneous melanoma cells to lung and lymph node, respectively. CCR6 is expressed in metastases from colon, ovarian and thyroid carcinomas to the liver where its ligand, CCL20, is constitutively expressed. As uveal melanomas frequently metastasize to the liver, we hypothesized that specific chemokine receptors and their respective ligands might be involved in metastasis of uveal melanoma to the liver. Methods:Tissue microarrays were constructed using 100 non irradiated primary uveal melanomas and 84 liver metastases, as well as 12 non liver metastases, collected from the files of Jules Gonin Eye Hospital and Pathology Institute, University of Lausanne. Immunohistochemistry was performed using anti-human CXCR4, SDF1, CCR7, CCL21 and CCR6 antibodies. Results:CXCR4 expression was detected in 36% of primary uveal melanomas and in 63% of liver metastases but no expression was found in metastases to other organs, except for one pancreatic metastasis. SDF1 expression was detected in 3% of primary uveal melanomas and in 26% of liver metastases, as well as in pancreas, lymph node and breast metastases. CCR6 expression was observed in the majority of primary uveal melanomas and liver metastases (73 and 88%, respectively). In addition, CCR6 was also detected in 9 metastases to other organs (pancreas, thyroid, lymph node, skin and breast). CCR7 and CCL21 were neither detected in primary uveal melanoma, nor in the metastases. Conclusions:Chemokine receptors CCR6 and CXCR4 are expressed in a large number of primary uveal melanomas and in uveal melanoma metastases to the liver. CCR6 is also expressed in a small number of metastases to other organs. These findings form the basis for further studies on the potential involvement of CXCR4 and CCR6 in the selective metastasis of uveal melanoma to the liver.

Intravitreal ranibizumab in the treatment of choroidal neovascularization associated with idiopathic central serous chorioretinopathy.

PURPOSE: We evaluate the functional and anatomic outcome after intravitreal ranibizumab treatment in patients with choroidal neovascularization (CNV) related to chronic central serous chorioretinopathy (CSC). METHODS: This is a small case series of 5 eyes with CNV associated with chronic CSC treated with intravitreal injection of 0.5 mg ranibizumab in the Jules Gonin University Eye Hospital from July 2007 to July 2009. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus examination, and optical coherence tomography (OCT). Fluorescein and indocyanine green angiography (ICG) were performed at baseline and repeated at least every 6 months. RESULTS: We studied 5 eyes of 4 patients with a mean age of 66 years. Mean follow-up was 21 months (SD 1.9). The mean number of intravitreal injections administered for each patient was 10 (SD 4.6). The mean initial BCVA was 0.23 (decimal equivalent) (logMAR 0.64, SD 0.13). At the last follow-up, mean BCVA was 0.44 decimal equivalent (logMAR 0.36, SD 0.31). Mean central macular thickness (CMT) measured with OCT was 330 microm (SD 43) at baseline and decreased at the final follow-up to 243 microm (SD 44 ). Persistent intraretinal or subretinal fluid on OCT and/or multifocal areas of increased choroidal permeability on ICG angiographies were present in all patients at the last follow-up visit. CONCLUSIONS: Intravitreal ranibizumab appeared to be an effective treatment of CNV related to chronic CSC. However, residual intraretinal or subretinal fluid and increased choroidal permeability persisted. Prospective controlled studies are warranted to evaluate the long-term safety and efficacy of intravitreal ranibizumab.

A history of the renewal of the corneal epithelium : a 3D animation

Background: To compare the different schemes that have been proposed during the last thirteen years to explain the renewal of the corneal epithelium. Material and Methods:We analyzed all the data present in the literature to explain the renewal of the corneal epithelium in mammals. According to the schemes proposed in the literature we developed a 3D animation to facilitate the understanding of the different concepts. Results:Three different schemes have been proposed to explain the renewal of the corneal epithelium in mammals during the last thirteen years. 1950-1981: the corneal epithelium was thought being renewed by mitosis of cells located in the basal layer. At this time scientist were not talking about stem cells. 1981-1986 was the period of the "XYZ hypothesis" or the transdifferentiation paradigm. At this time the conjunctival epithelium renewed the corneal epithelium in a centripetal migration. 1986-2008: the limbal stem cell paradigm, there were no stem cells in the corneal epithelium, all the corneal stem cells were located in the limbus and renewed the central cornea after a migration of 6 to 7 mm of transient amplifying cells toward the centre of the cornea. 2008, epithelial stem cells were found in the central cornea in mammals (Nature, Majo et al. November 2008). Discussion:We thought that the renewal of the corneal epithelium was completely defined. According to the last results we published in Nature, the current paradigm will be revisited. The experiments we made were on animals and the final demonstration on human has still to be done. If we find the same results in human, a new paradigm will be define and will change the way we consider ocular surface therapy and reconstruction.

Evaluating in vivo delivery of riboflavin with coulomb-controlled iontophoresis for corneal collagen cross-linking: a pilot study.

PURPOSE: To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). METHODS: The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran T500 solution (riboflavin-dextran) and 0.1% riboflavin 5'-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm(2) for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS: Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. CONCLUSIONS: Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.

Novel Cone Transducin Alpha Subunit Mutation In Tunisian Patients And Genotype-phenotype Correlation In Complete Achromatopsia

Purpose: Complete achromatopsia is a rare autosomal recessive disease due to CNGA3, CNGB3, GNAT2 and PDE6C mutations. We studied a large consanguineous Tunisian family including twelve individuals.Methods: Ophthalmic evaluation included a full clinical examination, color vision testing, optical coherence tomography and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing.Results: In all affected subjects, acuity ranged from 20/50 to 20/200. Fundus examination was normal except for two patients who had respectively 4 mm and 5 mm diameters of peripheral congenital hypertrophy. Likewise retinal layers exploration by OCT revealed no change in the thickness of the central retina. Color Vision with 100 Hue Farnsworth test described a profound color impairment along all three axes of color vision. The haplotype analysis of GNAT2 markers revealed that all affected offspring were homozygous by descent for the four polymorphic markers. The maximum lod score value, 4.33, confirmed the evidence for linkage to the GNAT2 gene.A homozygous novel nonsense mutation R313X was identified segregating with an identical GNAT2 haplotype in all affected subjects. This mutation could interrupt interaction with photoactivated rhodopsin, resulting in a failure of visual transduction. In fact, ERG showed a clearly abolished photopic b-wave and flicker responses with no residual cone function justifying the severe GNAT2 achromatopsia phenotype.Conclusions: This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and of the largest family with recessive achromatopsia involving GNAT2, thus providing a unique opportunity for genotype phenotype correlation for this extremely rare condition.

Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.

BACKGROUND: The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. METHODS: A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. RESULTS: 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). CONCLUSION: This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD).

OBJECTIVE: To identify a distinctive chronic visual complication of lysergic acid diethylamide (LSD) use. DESIGN: Description of the clinical findings in three patients with this disorder. SETTING: A neuro-ophthalmology referral center. RESULTS: All three patients experienced prolonged afterimages (palinopsia) during LSD intoxication and have continued to be symptomatic up to 3 years after they ceased to ingest the drug. Results of neuro-ophthalmologic and neurologic examinations and neuroimaging and electrophysiologic studies were normal. CONCLUSIONS: We have described three patients in whom persistent palinopsia developed following ingestion of LSD. Clinicians should inquire about past LSD use in all patients who initially have seemingly spontaneous, isolated palinopsia. Recognition of this distinctive clinical syndrome associated with LSD use might avoid unnecessary anxiety and excessive diagnostic tests for patients with this disorder.

Optimization Of Promoter Sequences In Order To Mimic Physiological Pde6b Expression

Purpose: Many retinal degenerations result from defective retina-specific gene expressions. Thus, it is important to understand how the expression of a photoreceptor-specific gene is regulated in vivo in order to achieve successful gene therapy. The present study aims to design an AAV2/8 vector that can regulate the transcript level in a physiological manner to replace missing PDE6b in Rd1 and Rd10 mice. In previous studies (Ogieta, et al., 2000), the short 5' flanking sequence of the human PDE6b gene (350 bp) was shown to be photoreceptor-specific in transgenic mice. However, the efficiency and specificity of the 5' flanking region of the human PDE6b was not investigated in the context of gene therapy during retinal degeneration. In this study, two different sequences of the 5' flanking region of the human PDE6b gene were studied as promoter elements and their expression will be tested in wild type and diseased retinas (Rd 10 mice).Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (150 bp) and -297 to +53 (350 bp)) were cloned in different plasmids in order to check their expression in vitro and in vivo by constructing an AAV2/8 vector. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP. jetPEI transfection in Y 79 cells was used to evaluate gene expression through luciferase activity. Constructs encoding EGFP under the control of the two promoters were performed in AAV2.1-93 (or 297)-EGFP plasmids to produce AAV2/8 vectors.Results: When pGL3-93 (150 bp) or pGL3-297 (350 bp) were transfected in the Y-79 cells, the smaller fragment (150 bp) showed higher gene expression compared to the 350 bp element and to the SV40 control, as previously reported. The 350 bp drove similar levels of expression when compared to the SV40 promoter. In view of these results, the fragments (150 bp or 350 bp) were integrated into the AAV2.1-EGFP plasmid to produce AAV2/8 vector, and we are currently evaluating the efficiency and specificity of the produced constructs in vivo in normal and diseased retinas.Conclusions: Comparisons of these vectors with vectors bearing ubiquitous promoters should reveal which construct is the most suitable to drive efficient and specific gene expression in diseased retinas in order to restore a normal function on the long term.

Whole anterior segment proton beam radiotherapy for diffuse iris melanoma.

AIM: To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma. METHODS: Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body. RESULTS: Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1-11.6 years). Tumour iris involvement was 1-4 h in five patients, 5-8 h in four and 9-12 h in three. Angle involvement was 6-8 h in five patients and 9-12 h in seven. The visual acuity (VA) before treatment was 6/5-6/6 in six patients, 6/8-6/9 in three and 6/18-6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5-6/9 in five patients, 6/18-6/24 in three, 6/60-1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures. CONCLUSIONS: Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.