Early effects of intravitreal triamcinolone on macular edema: mechanistic implication.

PURPOSE: To evaluate the early effects of intravitreal triamcinolone acetonide (TA) on cystoid macular edema associated with retinal vein occlusion and diabetic retinopathy. DESIGN: Prospective, interventional, small case series. PARTICIPANTS: Four patients with cystoid macular edema resulting from retinal vein occlusion or diabetic retinopathy of more than 4 months' duration and evaluated as suitable for treatment with intravitreous injection of TA. METHODS: After ophthalmic examination, including visual acuity assessment, intraocular pressure (IOP) measurement, and optical coherence tomography (OCT) analysis, the patients received a single intravitreal injection of 4 mg TA. After the injection, consecutive visual acuity assessment, IOP measurement, and OCT analysis were performed after 1 hour, 6 hours, 1 week, and 2 weeks. MAIN OUTCOME MEASURE: Optical coherence tomography assessment of macular thickness. RESULTS: Macular thickness and edema initially were reduced as early as 1 hour after TA injection. A further continuous decrease was observed during the 2 weeks after treatment. CONCLUSIONS: This rapid effect of intravitreal TA is interpreted to indicate that nongenomic effects on retinal or retinal pigment epithelial cell membranes, or both, may be responsible for this phenomenon. Identifications of these mechanisms may help design alternative, more specific drugs for the treatment of macular edema.

Short and longterm ocular vascular effects after intravitreal injection of ranibizumab for neovascular age-related macular degeneration

Purpose: To investigate the effect of the first and repeated intravitreal injections of ranibizumab (1.25mg; 0.05ml) on retrobulbar blood flow velocities in patients with wet age-related macular degeneration (AMD). Methods: This prospective non randomized study included twenty consecutive AMD patients. Time- averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before, 2 days and 3 weeks after the first injection of ranibizumab, then 6 months after supplemental monthly injections if required. At each visit, complete ophthalmological examination was performed, including best corrected visual acuity measurement according to ETDRS protocol and OCT. Results: In the treated eyes, ranibizumab injection was followed by a significant improvement in visual acuity (from 44.4 ± 21.7, to 50.9±25.9 (p<0.01) at month 6, and a decrease in mean central macular thickness from 377±115 to 267 ± 74 µm (p<0.001) at month 6. At day 2 mean BFVs decreased by 16% in the CRA and by 20% in TPCA (p<0.001, both), then remained stable. Mean BFVs did not change in OA at the day 2 but decreased at week 3 by 18% (p<0.001). Supplemental injections did not lead to additional effects at month 6. No effect was tabulated in the fellow eye. Conclusions: We report an early decrease in mean BFV in CRA and TPRA following intravitreal injections of ranibizumab corresponding to vasoconstrictive effect of this drug. Decrease in mean BFV in all retrobulbar arteries from the week 3 suggests that ranibizumab proceeds to a local and regional vasoconstrictive and antiangiogenic effects after local diffusion. Thus, ranibizumab could induce an actual hypoperfusion of the treated eye which could correspond to a vascular side effect.

Reemergence of dormant Coats disease after 30 years.

Purpose. We describe an atypical case of a patient with Coats disease that re-emerged after 30 years, illustrating a previously poorly understood long-term evolution of the disease. Methods. A 20-year-old man consulted for visual acuity (VA) decrease in the left eye (LE) to 0.3. Fundus examination revealed an exudative lesion with telangiectasias in the superior peripheral retina compatible with the diagnosis of Coats disease. Results. The patient was treated with cryotherapy and argon laser. Visual acuity improved to 0.5 and remained stable during a 1-year follow-up. The patient did not seek further clinical follow-up. Thirty years later, he returned complaining of a progressive VA decrease in the LE. Snellen VA was measured to counting fingers. Fundus examination revealed stage 3A Coats disease with macular exudation and a serous retinal detachment in the inferior quadrants requiring the placement of an encircling band, external drainage, and cryotherapy of the vascular lesions. After 10 additional sessions of argon laser on the vascular malformations, exudation regressed further and best-corrected VA increased to 0.1 at the end of the follow-up period. Conclusions. Coats disease must be considered as a chronic disease, which necessitates a very long-term follow-up even in the absence of subjective visual loss. The disease can reawaken and recur with force in previously unaffected areas of the retina several decades later. The gold standard treatment consists of cryotherapy and argon laser. However, in cases of very important retinal exudation, surgical management with subretinal drainage may be necessary.

Clinical spectrum of tuberculous optic neuropathy.

PURPOSE: Tuberculous optic neuropathy may follow infection with Mycobacterium tuberculosis or administration of the bacille Calmette-Guerin. However, this condition is not well described in the ophthalmic literature. METHODS: Ophthalmologists, identified through professional electronic networks or previous publications, collected standardized clinical data relating to 62 eyes of 49 patients who they had managed with tuberculous optic neuropathy. RESULTS: Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %), neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular tuberculosis was present. The majority of patients (69.4 %) had resided in and/or traveled to an endemic area. Although initial visual acuity was 20/50 or worse in 62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved visual acuities of 20/40 or better. Visual field defects were reported for 46.8 % of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up. CONCLUSION: Visual recovery from tuberculous optic neuropathy is common, if the diagnosis is recognized and appropriate treatment is instituted. A tuberculous etiology should be considered when evaluating optic neuropathy in persons from endemic areas.

Iontophoresis: from the lab to the bed side.

Pioneer work on iontophoresis undertaken by David Maurice during the 1970s and 1980s laid the initial groundwork for its potential implementation as a promising ocular therapeutic modality. A better understanding of tissue interactions within the eye during electric current application, along with better designs of drug delivery devices have enabled us to pursue David Maurice's original ideas and take them from the bench to the bed side. In the present study we demonstrate the potential application of an iontophoresis device (Eyegate, Optis, France) for the treatment of certain human eye diseases. Seventeen patients received a penetrating keratoplasty (PKP) at various intervals before presentation with active graft rejection in our clinic and were treated using this iontophoresis device. Methylprednisolone sodium succinate (MP) 62.5 mg/ml was infused within the Eyegate ocular probe container and an electrical current of 1.5 mA was delivered for 4 min with the negative pole connected to the ocular probe. Patients were treated on an ambulatory basis and received a standard course of three iontophoresis applications given once a day over 3 consecutive days. After treatment, 15 of the 17 treated eyes (88%) demonstrated a complete reversal of the rejection processes. In two eyes, only a partial and temporary improvement was observed. The mean best corrected visual acuity of all 17 patients during the last follow up visit was 0.37 +/- 0.2 compared to 0.06 +/- 0.05 before initiation of the iontophoresis treatment. The mean follow-up time was 13.7 months with a range of 5-29 months for the 17 patients. No significant side-effects associated with the iontophoresis treatment were observed. Thus, for the management of active corneal graft rejection, iontophoresis of MP can be an alternative to very frequent instillations of eye drops, or to pulsed intravenous therapy of corticosteroids.

Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature.

BACKGROUND: The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made. CASE PRESENTATION: Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas.Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes.Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243. CONCLUSION: Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing.

Outcomes of optic nerve sheath decompression for nonarteritic ischemic optic neuropathy.

Efficacy of optic nerve sheath decompression (ONSD) in treating non-arteritic ischemic optic neuropathy (NAION) is not clear. We retrospectively analyzed the records of 91 patients with NAION, who were examined during a two-year period, and compared the final Snellen visual acuities of eyes treated with ONSD with those of eyes that did not have surgery. Seven of 18 eyes with ONSD (39%) demonstrated increased visual acuity of two or more lines; whereas 23 of 71 eyes without surgery (32%) had increased acuity. The ONSD group and no surgery group were further subdivided into eyes with progressive visual loss and nonprogressive visual loss. No statistically significant differences in visual outcome between groups were found. We did not find the high frequency of visual improvement that has been reported in some studies of ONSD for NAION.

A novel homozygous R764H mutation in crumbs homolog 1 causes autosomal recessive retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP; MIM 268000) is a hereditary disease characterized by poor night vision and progressive loss of photoreceptors, eventually leading to blindness. This degenerative process primarily affects peripheral vision due to the loss of rods. Autosomal recessive RP (arRP) is clinically and genetically heterogeneous. It has been associated with mutations in different genes, including CRB1 (crumbs homolog 1). The aim of this study was to determine the causative gene in a Tunisian patient with arRP born to non-consanguineous parents. METHODS: Four accessible family members were included. They underwent full ophthalmic examination with best-corrected Snellen visual acuity, fundus photography and fluorescein angiography. Haplotype analysis was used to evaluate homozygosity in the family to 20 arRP loci. All exons and intron-exon junctions of candidate genes not excluded by haplotype analysis were PCR amplified and directly sequenced. RESULTS: The proband was a 43-year-old female patient. Best-corrected visual acuity was 20/63 (right eye) and 20/80 (left eye). Visual loss began during the third decade. Funduscopic examination and fluorescein angiography revealed typical advanced RP changes with bone spicule-like pigment deposits in the posterior pole and the midperiphery along with retinal atrophy, narrowing of the vessels, and waxy optic discs. Haplotype analysis revealed homozygosity with microsatellite markers D1S412 and D1S413 on chromosome 1q31.3. These markers flanked CRB1. Our results excluded linkage of all the other arRP loci/genes tested. Sequencing of the 12 coding exons and splice sites of CRB1 disclosed a homozygous missense mutation in exon 7 at nucleotide c. 2291G>A, resulting in an arginine to histidine substitution (p.R764H). CONCLUSIONS: R764H is a novel mutation associated with CRB1-related arRP. Previously, an R764C mutation was reported. Extending the mutation spectrum of CRB1 with additional families is important for genotype-phenotype correlations and characterization of the scope of mutation.

Endogenous ocular nocardiosis: an interventional case report with a review of the literature.

We present an illustrative case of endogenous ocular Nocardia (EON) infection in a man with Hodgkin disease treated by chemotherapy who underwent aggressive vitreoretinal surgery for diagnosis and treatment of a subretinal abscess. Visual acuity recovered from hand movements to 20/25. We review the 38 reported cases of EON published between 1967 and 2007, describe the clinical presentation from a systemic and ocular point of view, examine which ocular procedures were successful in identifying the bacterium, and analyze ocular morbidity and the factors affecting successful treatment.

Proton Therapy for Uveal Melanoma in 43 Juvenile Patients: Long-Term Results.

PURPOSE: To examine the metastatic and survival rates, eye retention probability, and the visual outcomes of juvenile patients after proton beam radiotherapy (PBRT) for uveal melanoma (UM). DESIGN: Retrospective case-factor matched control study. PARTICIPANTS AND CONTROLS: Forty-three patients younger than 21 years treated with PBRT for UM were compared with 129 matched adult control patients. METHODS: Information on patient demographics and clinical characteristics were recorded before and after treatment from patients' files. The control group was composed of adult patients (>21 years) matched for tumor size (largest tumor diameter, ±2 mm; height, ±2 mm) and anterior margin location (iris, ciliary body, pre-equatorial or postequatorial choroid). For each juvenile patient, 3 adults were selected. MAIN OUTCOME MEASURES: Comparing outcomes of juvenile and adult patients in terms of metastatic and eye retention rates using the log-rank statistic, relative survival using the Hakulinen method, as well as their visual outcomes. RESULTS: Forty-three juvenile and 129 control cases were reviewed. The metastatic rate at 10 years was significantly lower in juvenile UM patients than in adult controls (11% vs. 34%; P <0.01), with an associated relative survival rate of 93% versus 65% (P = 0.02). Six juvenile patients (14%) demonstrated metastases. One patient underwent enucleation because of a presumed local tumor recurrence and 4 additional patients underwent enucleation because of complications (9.3%). In the adult control group, 27% (n = 35) of matched patients demonstrated metastases, there were 2 cases of local recurrence, and 16% (n = 21) underwent enucleation because of complications. A visual acuity of more than 0.10 was maintained in most cases, without any significant differences before or after treatment observed between both groups. CONCLUSIONS: After PBRT, metastatic and survival rates are significantly better for juvenile than for adult patients with UM. Clinically, juvenile and adult eyes react similarly to PBRT, with patients having a comparable eye retention probability and maintaining a useful level of vision in most cases. This is the largest case-control study of proton therapy in juvenile eyes to date and further validates PBRT as an appropriate conservative treatment for UM in patients younger than 21 years.

Long-term results of deep sclerectomy with collagen implant.

PURPOSE: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI). SETTING: Glaucoma Unit, Department of Ophthalmology, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland. METHODS: This nonrandomized prospective trial comprised 105 eyes of 105 patients with medically uncontrolled primary and secondary open-angle glaucoma. Visual acuity, intraocular pressure (IOP), and slitlamp examinations were performed before surgery and after surgery at 1 and 7 days, and 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, 54, 60, 66, 72, 78, 84, 90, and 96 months. Visual field examinations were repeated every 6 months. RESULTS: Mean follow-up period was 64 months +/- 26.6 (SD). Mean preoperative IOP was 26.8 +/- 7.7 mm Hg, and mean postoperative IOP was 5.2 +/- 3.35 mm Hg at day 1 and 12 +/- 3 mm Hg at month 78. At 96 months, the qualified success rate (ie, patients who achieved IOP <21 mm Hg with and without medication) was 91%, and the complete success rate (ie, IOP <21 mm Hg without medication) was 57%. At 96 months, 34% of patients had an IOP <21 mm Hg with medication. Fifty-one patients (49%) achieved an IOP < or =15 mm Hg without medication. Neodymium:YAG goniopuncture was performed in 54 patients (51%); mean time of goniopuncture performance was 21 months, and mean IOP before goniopuncture was 20 mm Hg, dropping to 11 mm Hg after goniopuncture. No shallow or flat anterior chamber, endophthalmitis, or surgery-induced cataract was observed. However, 26 patients (25%) showed a progression of preexisting senile cataract (mean time 26 months; range 18 to 37 months). Injections of 5-fluorouracil were administered to 25 patients (23%) who underwent DSCI to salvage encysted blebs. Mean number of medications per patient was reduced from 2.3 +/- 0.7 to 0.5 +/- 0.7 (signed rank P<.0001). CONCLUSION: Deep sclerectomy with collagen implant appears to provide stable and reasonable control of IOP at long-term follow-up with few immediate postoperative complications.

Long-term close follow-up of chorioretinal lesions in presumed ocular tuberculosis.

PURPOSE: To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines. METHODS: Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOT TB test was performed when it became available. RESULTS: Visual acuity significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8 ± 20.9 (arbitrary units) and decreased to 32.5 ± 16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5 ± 13.3 and decreased to 10.8 ± 5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5 ± 1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively. CONCLUSIONS: A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.

Etude clinique et angiographique lors de la syphilis oculaire

UNIVERSITE DE LAUSANNE - FACULTE DE BIOLOGIE ET DE MEDECINE Médecine Ophtalmologie Etude clinique et angiographique lors de la Syphilis Oculaire THESE préparée sous la direction du Docteur Yan Guex-Crosier et présentée à la Faculté de biologie et de médecine de l'Université de Lausanne pour l'obtention du grade de DOCTEUR EN MEDECINE par Konstantinos BALASKAS Médecin diplômé de la Grèce Originaire d'Athènes (Grèce) ι Lausanne 2012  Une recrudescence des cas de syphilis a été observée ces dernières années. Son diagnostic clinique reste particulièrement difficile en l'absence de signe pathognomonique. Sur le plan oculaire elle présente un vaste spectre de manifestations diverses lui ayant valu le surnom de « la grande imitatrice ». Sa rareté et son hétérogénéité ont empêché l'identification et la vérification statistique des facteurs liés à un pronostic défavorable. Le but de cette étude a été d'explorer les paramètres cliniques et para-cliniques déterminant la sévérité et influençant l'évolution de la maladie. Ce travail comprend deux volets, la première partie intitulée : «Analysis of significant factors influencing visual acuity in ocular syphilis» publiée dans le British Journal of Ophthalmology a démontré qu'une mauvaise acuité visuelle initiale est associée de façon statistiquement significative à la sévérité de l'amputation du champ visuel, à la présence d'un oedème maculaire ou d'une neuropathie optique. Une amélioration de l'acuité visuelle grâce au traitement antibiotique est associée à la présence d'une vasculite (visible à l'angiographie fluorescéinique), d'une neurosyphilis ou d'une uvéite antérieure. Une récidive inflammatoire est fortement associée à une durée prolongée des symptômes avant l'introduction du traitement et à la présence de douleur comme signe d'appel. L'utilité clinique principale de ces résultats statistiques permet de conclure que les formes inflammatoires sévères associées à la triade (vasculite, neurosyphilis et uvéite antérieure) constituent un phénomène réversible pour autant qu'un traitement précoce et adéquat ait été introduit. Le deuxième volet de l'étude analyse les manifestations angiographiques (à la fluorescéine (AF) et au vert d'indocyanine (AICG)) de la syphilis oculaire et a été publié dans le journal du Graefes Archives of Clinical and Experimental Ophthalmology sous le titre suivant : "Fluorescein and indocyanine-green angiography in ocular syphilis: an exploratory study". Des associations faibles ont été démontrées entre la présence d'une vasculite lors de AF et d'une uvéite antérieure, d'une hyalite et d'un âge plus jeune. Une association forte est identifiée entre la présence des «dark dots» sur l'AICG et d'une uvéite antérieure ainsi qu'entre la présence des «hot spots» sur l'AICG et d'une durée prolongée des symptômes. Les conclusions d'importance clinique significative lors de la syphilis oculaire sont que les « dark dots » ou hypofluorescences en AICG évoquent la présence d'une atteinte inflammatoire oculaire sévère et que les « hot spots » ou hyperfluorescences en AICG sont significatifs d'une atteinte chronique. Cette étude contribue à modifier les attitudes cliniques lors de la syphilis oculaire surtout en ce qui concerne l'urgence à traiter afin d'assurer une récupération optimale. Elle aide aussi à redéfinir le rôle de l'angiographie dans la syphilis oculaire pour déterminer la sévérité, la durée de la maladie ainsi que le pronostic visuel.

Metastatic choroidal paraganglioma.

PURPOSE: To describe a patient with metastatic choroidal paraganglioma that was locally controlled with radiotherapy. DESIGN: Interventional clinicopathologic case report. PARTICIPANT: One patient with metastatic choroidal paraganglioma. METHODS: Interventional clinicopathologic case report and systematic search of the literature. MAIN OUTCOME MEASURES: Description of clinicopathologic features, treatment methods, and outcome. RESULTS: A 50-year-old man had a nonpigmented atypical choroidal mass with secondary retinal detachment in the left eye. After incisional biopsy, the diagnosis of paraganglioma was established. Metastatic work-up revealed vertebral, mediastinal, and pulmonary metastases of a nonsecretory, malignant paraganglioma without tracer uptake. The primary tumor was not identified. The ocular tumor regressed after stereotaxic radiotherapy. Two years later, recurrent lesions developed in the contralateral eye, which also was irradiated. CONCLUSIONS: Malignant paraganglioma can metastasize in the choroid and should be included in the differential diagnosis of a nonpigmented choroidal mass. Stereotaxic radiation therapy is an effective treatment method. To the authors' knowledge, this is the first report of a patient with choroidal paraganglioma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.