Visual acuity and factors influencing automobile driving status in 1,000 patients age 60 and older.

BACKGROUND: The objective of this prospective observational study was to evaluate the number of people driving in accordance with common legal standards, measured through far binocular visual acuity, and to identify variables associated with driving habits outside of legal standards. METHODS: Subjects aged 60 years and older were recruited at a tertiary referral center (University Hospital of Mont-Godinne, Yvoir, Belgium). Ophthalmological examination was conducted in all subjects by an ophthalmologist. Visual acuity was measured with the modified Early Treatment Diabetic Retinopathy charts at a distance of 4 m on each eye for far binocular visual acuity, defined as equal or better than 20/40, according to the European legal driving requirements. Details on demographic, socioeconomic, and medical characteristics were obtained from all participants by questionnaires. Numerical variables were compared with the Wilcoxon rank sum test. Categorical and ordinal parameters were compared with the Chi-square test or the Cochran test respectively. RESULTS: One thousand subjects (447 women and 553 men) were enrolled in the study over a period of 7 months (mean age: 71.3 ± 8.8 years), of whom 810 were current drivers. Among the 810 current drivers, 732 (90.4 %) had a far binocular visual acuity equal or better than 20/40 (mean 0.89), and 78 (9.6 %) did not (mean 0.36). Among the 190 non-drivers, 94 (49.5 %) never drove; 47 (24.7 %) had stopped driving because of their impaired vision; and 49 (25.8 %) had stopped driving for other reasons. A logistic regression was performed to identify the variables statistically associated with the practice of driving among licensed drivers without minimal visual requirements, which revealed that a non-recent ophthalmological examination (p < 0.001), the subject's non-perception of impaired vision (p = 0.001), and non-access to stores without a car (p < 0.001) were influencing factors. CONCLUSIONS: In our study, 81 % of subjects aged 60 years and older were still driving, of whom 10 % did not meet the European legal driving requirements set at equal or better than 20/40. The variables associated with driving status were the time of last examination, non-perception of a visual impairment, and limited access to stores without a car.

Conjunctival nevi clinical features and therapeutic outcomes.

OBJECTIVE: To determine the epidemiology and the clinical and therapeutic outcomes of conjunctival nevi and to identify the clinical variables statistically associated with operative excision. DESIGN: Prospective, observational, noncomparative case series. PARTICIPANTS: Two hundred fifty-five patients with the clinical diagnosis of conjunctival nevus. METHODS: Consecutive cases of conjunctival nevi managed at a single institution were studied to identify the clinical risk factors for operative excision. MAIN OUTCOME MEASURES: Reasons for operative excision. RESULTS: Of the 255 patients who were periodically observed for a mean of 5.3 years (range, 1-11), nevi were clinically diagnosed in 140 females and 115 males and modified operative excision was performed in 75 patients (29%). The decision of operative excision was made by the surgeon in 13 cases (17%) and by the patient in 62 cases (83%). In those 13 patients, the operative decision was prompted by our concern for possible malignant transformation based on suspicious biomicroscopic features in 10 patients (13%) and photographically documented tumor growth in 3 patients (4%). For the other 62 patients who elected to undergo surgery, their reasons for excision included patient's concern for cancer in 34 cases (45%), cosmetic arguments in 9 cases (12%), and patient's request owing to lesion-induced ocular surface irritation in 19 cases (25%). Comparison between groups showed that the clinical factors at initial visit that were statistically predictive of surgical excision were the older age of the patient (P = 0.001), the largest basal tumor diameter (P<0.001), tumor location (P = 0.023), and presence of clear cysts (P = 0.013), of intrinsic vasculature (P<0.001), of prominent feeder vessels (P<0.001), and of corneal involvement (P = 0.008). None of the excised lesions showed histopathologically malignant features. CONCLUSIONS: In our series, documented tumor growth of conjunctival nevus remained relatively a uncommon event with a incidence of 4%. Conjunctival nevi in older patients, associated with dilated feeder vessels, prominent intrinsic vasculature, and corneal involvement were more likely to be treated with operative excision. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Cytomegalovirus retinitis after low-dose intravitreous triamcinolone acetonide in an immunocompetent patient: a warning for the widespread use of intravitreous corticosteroids.

We report the case of an immunocompetent 78-year-old woman who developed cytomegalovirus (CMV) retinitis after a single intravitreous injection of triamcinolone acetonide (IVTA). Review of medical records. The patient with macular edema secondary to branch retinal vein occlusion developed peripheral retinitis with hemorrhagic and inflammatory vascular sheathing 3 months after IVTA. A presumptive diagnosis of viral retinitis was confirmed by polymerase chain reaction (PCR) of the aqueous humor tap. The PCR test was positive for CMV DNA. The patient slowly responded to intravenous ganciclovir and oral valganciclovir. After therapeutic vitrectomy for intercurrent vitreous hemorrhage, and while still under treatment, the retinitis resolved completely with final visual acuity of 20/25. CMV retinitis can occur after local immunosuppression with IVTA in an immunocompetent patient with no other systemic risk factors.

DNA alteration-based classification of uveal melanoma gives better prognostic stratification than immune infiltration, which has a neutral effect in high-risk group.

BACKGROUND: In uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra-tumor immune population, compare it to other established biomarkers and to patients' outcome. METHODS: Primary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed using: transcriptomic profiling (n = 15), RT-qPCR (n = 36), immunohistochemistry (n = 89), Multiplex Ligation-dependent Probe Amplification (MLPA) for copy number alterations (CNA) analysis (n = 89), array-CGH (n = 17), and survival statistics (n = 86). RESULTS: Gene expression analysis divided uveal melanomas into two groups, according to the IFNγ/STAT1-IRF1 pathway activation. Tumors with IFNγ-signature had poorer prognosis and showed increased infiltration of CD8+ T lymphocytes and macrophages. Cox multivariate analyses of immune cell infiltration with MLPA data delineated better prognostic value for three prognostic groups (three-tier stratification) than two (two-tier stratification). CNA-based model comprising monosomy 3, 8q amplification, and LZTS1and NBL1 deletions emerged as the best predictor for disease-free survival. It outperformed immune cell infiltration in receiver operating characteristic curves. The model that combined CNA and immune infiltration defined risk-groups according to the number of DNA alterations. Immune cell infiltration was increased in the high-risk group (73.7%), where it did not correlate with patient survival, while it was associated with poorer outcome in the intermediate risk-group. CONCLUSIONS: High degree of immune cell infiltration occurs in a subset of uveal melanomas, is interferon-gamma-related, and associated with poor survival. It allows for two-tier stratification, which is prognostically less efficient than a three-tier one. The best prognostic stratification is by CNA model with three risk-groups where immune cell infiltration impacts only some subgroups.

Retinoblastoma and deletion of the long arm of chromosome 13: an underestimated diagnosis?

We report an infant with normal neurological development and phenotype who developed bilateral retinoblastoma (RB). This patient, despite lack of dysmorphic features, demonstrated constitutional abnormality of the long arm of chromosome 13 on standard karyotype. We recommend systematic cytogenetic examinations complemented by fluorescent in situ hybridization as second-line screening in all patients suspected for hereditary RB despite negative RB1 molecular screening and normal phenotype.

Unilateral retinoblastoma, lack of familial history and older age does not exclude germline RB1 gene mutation.

Conclusive identification of RB1 mutations in retinoblastoma is predicted to improve the clinical management of affected children and relatives. However, despite clear clinical benefits, RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutional RB1 analysis undertaken in our institution over the last four years. The detection of RB1 gene deletion or mutation was performed by Southern blot and sequence analyses in 73 patients (including three families with 2, 3 and 3 probands, respectively). Complementary constitutional chromosome and fluorescent in situ hybridization (FISH) analyses of RB1 gene were applied in cases where hereditary retinoblastoma was suspected despite negative detection. Altogether, germline abnormalities were found in 11% (4/36 patients) of sporadic unilateral retinoblastoma (median age, 21.5 months) and 86% (32/37 patients) of sporadic bilateral or positive familial history retinoblastoma (median age, 5 months). The spectrum of germline alterations found in 31 distinct families included 12 nonsense mutations (39%); 10 point insertions or deletions with frameshift (32%); 4 mutations and 1 deletion affecting splice sites (16%); 2 missense mutations (6%); and 2 large deletions (6%). A total of 15 mutations have not been previously reported. In this small series, splicing mutations were associated with bilateral disease whilst most of the frameshift mutations were identified in patients with an early age at diagnosis, bilateral disease or hereditary forms of the disease. This study confirms that screening for constitutional RB1 mutation should become an integral part of current management of any patient affected by retinoblastoma irrespective of the tumour laterality and familial background.

Primary orbital melanoma treated with iodine-125 plaque radiotherapy.

PURPOSE: To report a case of primary orbital melanoma successfully managed by custom-designed iodine-125 plaque. DESIGN: Case report. METHODS: A 59-year-old man with no systemic or secondary melanocytic tumor was diagnosed with primary orbital melanoma after transconjunctival incisional biopsy. He was treated with unshielded iodine-125 plaque (90 Gy) that was sutured to the sclera. The radiation plan was calculated to safely target the initial tumor volume and any residual intrascleral or loose orbital melanoma cells that could have been disseminated to the surrounding orbital tissues during incisional biopsy. RESULTS: After 66 months' follow-up, the patient was still alive with partial remission of his liver metastases. Routine orbital magnetic resonance imaging studies confirmed the lack of orbital recurrence. CONCLUSIONS: Plaque radiotherapy appears to be a reasonable alternative to exenteration or external irradiation for orbital melanoma after biopsy confirmation.

Intraorbital implantation of a stimulating electrode for an optic nerve visual prosthesis. Case report.

Research into visual prosthetics is expected to revolutionize the treatment of blind patients with incurable outer retinal degenerative disease. Substantial evidence shows that useful visual sensations can be produced by controlled electrical stimulation of the optic nerve. To make the optic nerve visual prosthesis more acceptable, implantation techniques safer and less invasive than those previously used have been developed. A medial transconjunctival approach is now used to implant a stimulating electrode around the intraorbital section of the optic nerve. This new technique allows sufficient exposure of the nerve after detaching only one rectus muscle and performing a lateral canthotomy. Previously, an electrode was implanted in the intracranial part of the optic nerve, which required more invasive surgery. The new technique was first developed in cadavers and in patients undergoing eye enucleations. Finally, a 68-year-old blind man suffering from retinitis pigmentosa underwent long-term implantation. In this case report the authors describe the technique and outline some of the challenges involved.

Anterior segment imaging using optical coherence tomography and ultrasound biomicroscopy in secondary pigmentary glaucoma associated with in-the-bag intraocular lens.

A 43-year-old man with high myopia developed unilateral pigmentary glaucoma with recurrent episodes of painless blurred vision in the left eye following uneventful phacoemulsification. Bilateral cataract surgery was performed with capsular bag implantation of a +4.00 diopter AcrySof MA60 intraocular lens (IOL) (Alcon Laboratories) followed by a neodymium:YAG laser capsulotomy. Secondary iatrogenic dispersion syndrome in the left eye with subsequent intraocular pressure elevation was suspected in the presence of anterior chamber pigmented cells, circular epithelial iris loss around the pupil, and trabecular hyperpigmentation. Close contact between the edge of the IOL and the posterior pigmented iris epithelium, which was clinically suggested by anterior biomicroscopy, was documented by ultrasound biomicroscopy and optical coherence tomography of the anterior segment.

Structure and function of the N-cadherin/catenin complex in retinoblastoma.

PURPOSE: To identify in human retinoblastoma and normal retinal tissue the type of cadherin, its relationship with cytoplasmic catenins, and its participation in invasion. METHODS: The cadherin/catenin complex was characterized in surgical retinoblastoma specimens from five patients and human retinas from four donor eyes by immunocytochemistry, flow cytometry, and coimmunoprecipitation with antibodies against N-cadherin, alpha-catenin, and beta-catenin, followed by Western blot analysis or autoradiography. Y79 and WERI-Rb-1 retinoblastoma cell lines serve the evaluation of the cadherin/catenin complex in aggregation and collagen type I invasion in vitro. The association of the cadherin/catenin complex with the cytoskeleton was examined by an antibody-capping assay. RESULTS: In retinoblastoma and normal retina N-cadherin associated with alpha-catenin and beta-catenin but not E- or P-cadherin. The N-cadherin/catenin complex formed a regular, linear, and continuous honeycomb pattern in normal retina that was irregular, clustered, and interrupted in retinoblastoma. The N-cadherin/catenin complex was found also in the retinoblastoma cell lines WERI-Rb and Y79, in which it also showed an irregular pattern. Both cell lines were invasive in collagen type I, and invasion was inhibited by the GC-4 antibody, which functionally neutralizes N-cadherin. Less GC-4 antibody was needed to inhibit invasion of Y79 cells, which expressed N-cadherin at a lower level, than to inhibit invasion of WERI-Rb-1 cells. In both cell lines, antibody capping of the N-cadherin/catenin complex indicated that its linkage with the cytoskeleton were weak or absent. CONCLUSIONS: Retinoblastoma cells, in contrast with normal retina, express an N-cadherin/catenin complex that is irregularly distributed and weakly linked to the cytoskeleton. In retinoblastoma, this complex acts as an invasion promoter.

Porous polyethylene orbital implant in the pediatric population.

PURPOSE: To determine the incidence of complications of primary insertion of porous polyethylene orbital implant in the pediatric population. DESIGN: Interventional case series. METHODS: Prospective nonrandomized case series of 36 eyes of 36 patients under age 15 years who underwent primary placement of an anteriorly wrapped spherical porous polyethylene orbital implant from March 1998 to August 2002, with at least 17 months of follow-up. RESULTS: The mean age at the time of surgery was 4.6 years. The histopathologic diagnoses after enucleation included intraocular tumor in 22 patients, phthisis bulbi in eight patients, microphthalmos in three patients, Coats disease in two patients, and ruptured traumatic globe in one patient. Twelve patients (33%) had prior ocular surgery. At the time of enucleation, all patients underwent primary placement of spherical porous polyethylene orbital implant anteriorly wrapped with homologous sclera in 30 patients (83%) and autologous sclera in six patients (17%). The spherical implant size was 16 mm in one patient (3%), 18 mm in 10 patients ( 28%), and 20 mm in 25 patients (69%). The prosthesis was fitted after a mean interval of 5 weeks. After a mean follow-up of 44 months (range, 17 to 68 months), there was one case of pyogenic granuloma (3%) and one case of implant exposure (3%). There were no cases of implant extrusion, superior sulcus syndrome, orbital cellulitis, or significant inflammatory response. No porous polyethylene orbital implant was drilled for peg placement. CONCLUSIONS: Anteriorly wrapped primary porous polyethylene orbital implant in the pediatric population appears to be well tolerated with few complications.

Allergic contact dermatitis following ocular use of corticosteroids.

AIM: To study the clinical features and to identify the molecules responsible for contact-allergic reactions following ocular use of corticosteroid (CS) preparations. DESIGN: Observational case series. METHODS: We reviewed the clinical data, the patch test results, and sensitization sources in patients with a CS contact allergy, who have been patch tested in the K.U. Leuven Dermatology department during an 18-year period. RESULTS: Eighteen subjects (out of 315 with CS delayed-type hypersensitivity) presented with allergic manifestations (conjunctivitis, eczema of the face, periocular skin or eyelids) of delayed-type hypersensitivity reactions to the use of CS-containing ocular preparations. The most common allergen was hydrocortisone, but most patients presented with multiple positive tests, not only to other CSs, but also to other active principles, preservatives, and vehicle components. CONCLUSIONS: Ophthalmic CSs, despite their anti-inflammatory and antiallergic properties, may produce contact-allergic reactions.

Atypical spherical deposition on vitreoretinal interface associated with toxoplasmic chorioretinitis.

PURPOSE: To report the clinical and optical coherence tomography features of spherical deposits associated with recurrent toxoplasmic chorioretinitis. METHODS: Case report. RESULTS: Atypical, 100 microm to 150 microm, greyish deposits appeared along retinal arteries and veins as well as on the vitreoretinal interface in the macula of a 44-year-old Caucasian woman while she was being treated for recurrent toxoplasmic chorioretinitis with antiparasitic drugs and subconjunctival injection of betamethasone. They disappeared progressively with the systemic use of corticosteroids. Their clinical course was nicely documented by optical coherence tomography. CONCLUSIONS: Greyish spherical deposits on the vitreoretinal interface have been previously described as inflammatory reactions in asymptomatic human T-lymphotropic virus type I (HTLV-1) carriers and in patients with HTLV-1-associated uveitis. For the first time, optical coherence tomography (OCT) provided clinical correlation of this unusual presentation of toxoplasmic chorioretinitis.

Choroidal metastasis from carcinoma of the bladder.

PURPOSE: To report choroidal metastasis from the newly described nested variant of urothelial carcinoma of the bladder as the initial presentation of metastatic disease. METHODS: A 58-year-old man with a history of urothelial bladder carcinoma developed progressive decreased visual acuity in the right eye. Fundus examination showed an amelanotic choroidal tumor simulating a choroidal melanoma. Results of ancillary diagnostic tests, needle aspiration biopsy, and systemic workup failed to confirm the diagnosis of choroidal metastasis. The patient was treated with enucleation the affected right eye. RESULTS: Histopathologic analysis of the enucleated eye disclosed a choroidal metastatic carcinoma with urothelial features similar to those of the bladder carcinoma excised previously. Despite adjuvant systemic chemotherapy, the patient died 7 months after enucleation. CONCLUSION: Choroidal metastasis may be the initial manifestation of metastatic bladder carcinoma and is associated with a poor survival prognosis.

Physiological diurnal variability and characteristics of the ocular pulse amplitude (OPA) with the dynamic contour tonometer (DCT-Pascal).

PURPOSE: The Pascal dynamic contour tonometer (DCT) allows measurement of intraocular pressure (IOP) independently of corneal properties. It records, simultaneously, haemodynamic IOP fluctuations and the difference between the systolic and the diastolic IOP corresponding to the ocular pulse amplitude (OPA). The OPA indirectly reflects choroidal perfusion and could be considered as an independent risk factor in glaucoma. We aimed to establish the physiological diurnal variability of the OPA and its correlations with other biophysical parameters because its characteristics remain partly unclear. METHOD: Prospective study including 52 eyes of 28 normal subjects with Goldmann applanation tonometry (GAT) IOPs < 22 mmHg. Subjects treated with systemic medications that could interfere with blood pressure or heart rate were excluded. IOP was measured at 9:00 am, 1:00 pm, and 4:00 pm by GAT and DCT. Two consecutive GAT followed by three consecutive DCT measurements were performed in each session by the same clinician (SP). Only DCT measurements with quality 1 and 2 were taken into account. Blood pressure, pulse rate, and central corneal thickness (CCT) were recorded after the last IOP measurements. Spearman correlation coefficient was used for assessment of correlations. RESULTS: Mean age was 40 +/- 14 years. Mean DCT values were significantly higher than GAT readings (mean = 16.8 +/- 2.0 vs. 15.2 +/- 2.8 mmHg, P < 0.02). The mean OPA was 2.2 +/- 0.7 mmHg (range: 1-3.4 mmHg). The mean amplitude of diurnal OPA fluctuations was 0.4 mmHg. There was no significant difference in the mean OPA values at each time of the diurnal curve. The intraclass correlation (ICC) of only one OPA measurement in relation to part of total variance due to inter-measurement variation was 78%. Averaging over three independent readings of OPA improved ICC to 91%. The OPA was correlated with GAT (r = 0.31, P < 0.0001) and DCT IOP measurements (r = 0.49, P < 0.0001). It was correlated neither with blood pressure nor with age. OPA values of both eyes of the same individual were highly correlated (r = 0.89, P < 0.0001). CONCLUSION: In normal healthy eyes, the ocular pulse amplitude remains stable during normal outpatient office hours and was not correlated with blood pressure or age of patients.

Susac syndrome in four male patients.

PURPOSE: To report the clinical and imaging features in four male patients presenting with Susac syndrome, a microangiopathy affecting the brain, the retina, and the cochlea. METHODS: Retrospective review of clinical data, fluorescein angiograms, and magnetic resonance imaging findings in these four cases. RESULTS: All four patients were young men (range, 20-35 years). The axiomatic triad of ocular, cochlear, and neurologic involvement was present in three patients. Neurologic symptoms were absent in the fourth one. Fluorescein angiography showed arteriolar wall hyperfluorescence in all four patients. Magnetic resonance images showed in three patients multifocal hyperintense lesions in the white matter and the corpus callosum with typical involvement of the central fibers. Therapeutic modalities and clinical course are described. Three patients had a follow-up of 3, 5, and 13 years with complete remission of the disease within 1 year in all three cases. One patient had severe neuropsychological sequelae. CONCLUSION: Susac syndrome seems to be less unusual in men than previously reported. Though presenting as a self-limited monophasic course disease in most cases, it may result in severe neuropsychological sequelae. Early diagnosis of the syndrome is enabled by the combination of the ophthalmologic, audiometric, and brain magnetic resonance features.