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AIMS/PURPOSE To investigate Leber congenital amaurosis (LCA) patients' expectations, decision-making processes and gene therapy-related concerns. METHODS Using a qualitative approach, we explored perceptions of gene therapy and clinical trials among individuals with LCA. Young adults with a clinical diagnosis of LCA were recruited through the Ocular Genetics Programme at the Hospital for Sick Children. Semi-structured interviews were conducted with ten patients and analysed following the principles of qualitative description. RESULTS Study participants were aware of ongoing gene therapy research trials and actively sought information regarding advances in ophthalmology and vision restoration. The majority of participants would enrol or were enrolled in a gene-replacement therapy trial, while a minority was ambivalent or would not enrol if provided an opportunity. Participants attributed different values to clinical trials, which influenced their willingness to participate. Intrinsic factors related to coping, adaptation to vision loss and resilience also influenced decision-making. DISCUSSION This study highlights the complex factors involved in gene-therapy-related decision-making and acts as a proponent for adopting patient-centred care strategies when counselling individuals considering gene therapy or clinical trial participation.

Genetic eye diseases (GEDs) are clinically and genetically heterogeneous. Results from molecular genetic testing are redefining the etiology and clinical spectrum of these heritable diseases, helping to explain the observed overlap in clinical phenotypes. Patients and parents benefit from DNA analysis when results confirm a diagnosis or make a diagnosis more specific. Accurate counseling can then be provided regarding the prognosis, presymptomatic diagnosis, life and family-planning issues and whether to anticipate other ocular or systemic medical problems. Patients hope that mutation identification will enable their participation in future clinical trials for treatment. Requests for molecular testing are increasing while those in the visually impaired world and the healthcare professionals who manage them wait to learn long-term results of the first human clinical trials for a GED to be treated with gene therapy, RPE65-type Leber congenital amaurosis. The advantages and disadvantages of molecular testing...

Background: Patients who suffer from ocular genetic diseases have special needs in terms of diagnosis and management of rare entities, low-vision needs, genetic counselling, and psychosocial adjustments that are usually not addressed by an ophthalmologist alone.The Ocular Genetics Program (OGP) at the Hospital for Sick Children,Toronto, was established in 1994 to provide comprehensive, multidisciplinary care of patients with inherited eye disorders.We now assess the benefits of such a program and of integrating research into the care of patients. Methods: We report our experience in developing a multidisciplinary ocular genetics program and the results of a pilot patient satisfaction survey that involved 61 patients. Results: The OGP multidisciplinary aspects are described. Of the 61 patients surveyed, 98% stated that they were satisfied with the OGP; 93%–96% of patients were content with "one day of appointments","understanding of eye problem", and "coordination of ancillary tests such as visual fields test, electrophysiology, and others"; and for 70%–86% of respondents "waiting time to get an appointment", "information received on current research", and "primary health care provider adequately informed" were satisfactory. Interpretation: The OGP is a unique service in Canada, which strives to provide the comprehensive care needed by ocular genetic patients.High patient satisfaction is an indicator of the success of this approach. Long waiting times for appointments and application of laboratory research in clinical care remain challenging.

To investigate psychosocial adjustment to visual loss in patients with retinitis pigmentosa (RP).Cross-sectional study.Thirty-three legally blind patients with RP participated in the study. Information regarding the patients' adjustment to their visual loss was obtained using the Psychological Adjustment to Illness Scale (PAIS-SR). Seven psychosocial domains were tested: health-care orientation, vocational environment, domestic environment, sexual relationships, extended family relationships, social environment, and psychological distress. These scores were compared with the psychosocial adjustment of patients with diabetes.Significantly elevated scores (a high score reflecting poor adjustment) were seen in four out of seven domains. The highest relative score was seen in the health-care orientation domain (65 +/- 14, p0.001), followed by vocational function (61 +/- 11, p0.001), social environment (58 +/- 9, p0.001), and extended family relationships (55 +/- 9, p0.05). The total PAIS score was significantly elevated (58 +/- 8; p0.001).Patients with RP have difficulties in adjusting to their visual loss particularly with respect to health-care orientation, vocational environment, social environment, and extended family relationships. They face more difficulties in these domains than diabetic patients in adjusting to their illness.

Purpose of review To introduce the issues specific to the genetic counseling profession for genetic eye diseases. Recent findings To discuss current issues in ocular genetic counseling including the use of a focused ophthalmology pedigree, informed consent in the blind population, genetic testing trends and psychosocial issues. Summary Introduce the time-consuming issues to be addressed in genetic counseling for genetic eye disease patients.

Two-thirds of retinoblastoma cases are unilateral, with most presenting with an advanced stage of disease. Primary enucleation is usually the preferred treatment. Conservative therapy may save less involved eyes.We retrospectively reviewed the presentation, age at diagnosis, classification, genetic status, treatment, and long-term outcome of 130 patients with unilateral retinoblastoma (1988-2008).The mean age at presentation was 26 months. Based on retinoblastoma gene (RB1) status in tumors, germ-line status was defined in 92% of patients; 13% had a germ-line mutation. The primary treatment of 106 patients was enucleation. Severe disease at presentation (International Intraocular Retinoblastoma Classification [IIRC] group E) was significantly (p0.001) associated with adverse histopathological risk factors. Of the 16 patients who underwent eye-conserving therapy, treatment was successful in 9 (IIRC group A, 1; B, 5; C, 3). Two patients with a pertinent family history were diagnosed early and were treated solely with focal therapy. Three patients retained vision of 6/18 or better in the treated eye (median follow-up, 33 months; range, 2-120 months). Seven patients (IIRC group: B, 2; C, 4; D, 1) eventually underwent enucleation. One patient died of metastases following delayed parental consent for enucleation and refusal of prophylactic chemotherapy for high-risk histopathologic features.Chemotherapy/focal therapy can save selected eyes, but primary enucleation is preferred for advanced unilateral retinoblastoma. "Conservative" treatment is an option when there is good potential for useful vision without prolonged, costly therapy with potential side effects. Simple enucleation reduces the risk of masking high-risk pathology and promotes early return to normal life.

RESUME Background: The purpose of this study was to describe our experience with the clinical effects of molecular genetic testing for retinitis pigmentosa (RP) and related retinal dystrophies. Methods: Chart review of 303 consecutive patients with retinal dystrophies was done when blood was sent for molecular genetic testing between 1993 and 2001. Phenotype information was retrieved for patients with identified mutations. The yield of positive and clinically useful results was assessed. Results: Participants comprised 35 patients with Leber congenital amaurosis, 18 with Usher syndrome, and 250 with isolated RP or other retinal dystrophies. Of these 303 participants, 203 (67%) received positive or negative results of molecular testing for an average of 2.7 genes. Positive results were available in 19 patients after an average time interval of 38 ± 22 months (median 33 months, range 1-89 months). No results were received for 84 (28%) patients. In 16 (5%) cases, patients received partial results. Only 19 (6%) patients were found to have sequence changes in RHO, RDS, CRB1, or USH2A, 2 of which were thought to be disease-causing. Only 2 sequence changes were previously documented mutations, but several other novel changes were suspected to be disease-causing mutations also. Interpretation: Molecular testing was helpful only in the minority of cases, largely because of a lack of availability, as well as the complexity of the molecular genetics of RP. Improvements in funding, infrastructure, and molecular knowledge will be necessary to improve the transformation of molecular genetic testing into a clinically relevant bedside tool.

Ocular albinism type 1 (OA1) is an X-linked disorder, mainly characterized by a severe reduction in visual acuity, foveal hypoplasia, nystagmus, hypopigmentation of the retina, the presence of macromelanosomes in the skin and eyes, and the misrouting of optic pathways, resulting in the loss of stereoscopic vision. We screened the OA1 gene for mutations in three unrelated Canadian and French families and in two isolated patients with OA1. We found three different missense mutations and two different nonsense mutations, three of which were novel. To date, 41 mutations (including missense mutations, insertions, and deletions) have been reported in the OA1 gene. Mutation and polymorphism data for this gene are available from the international albinism center albinism database website: http://www.cbc.umn.edu/tad/oa1map.htm.

Congenital glaucoma refers to a genetically heterogeneous group of distinctive clinical diseases characterised by increased intraocular pressure most often associated with increased corneal diameter, corneal oedema, and consequent visual impairment. Primary congenital glaucoma (PCG) is associated with a primary angle defect, whereas secondary congenital glaucoma is associated with a more generalised developmental anomaly of the anterior segment such as seen in Peters' anomaly. The inheritance of PCG is usually autosomal recessive. Peters' anomaly consists of corneal opacity, defects in the posterior structures of the cornea, and iridocorneal and/or keratolenticular adhesions, and it most frequently occurs sporadically.1Over 50% of subjects develop glaucoma in childhood. Numerous aetiologies have been proposed including chromosomal abnormalities, teratogens,1 and mutations in the eye developmental genes PAX6 2-4 and PITX2 .5 However, large subsets of Peters' anomaly cases are without molecular characterisation. Primary congenital glaucoma has been linked to chromosomes 1p36 (GLC3B) and 2p21 (GLC3A), but only the GLC3A gene has been identified. This gene, CYP1B1 , encodes a broadly expressed cytochrome P450 enzyme (P4501B1) whose natural substrate is unknown.6 7 It is proposed to be the major gene for disease causing mutations in primary congenital glaucoma.6-11 A variety of chain terminating and missense CYP1B1 mutations have been described.6-9 We report two novel mutations in CYP1B1 in a patient who had Peters' anomaly with secondary congenital glaucoma. The subject, a male of Native Indian (Mohawk)/French Canadian background, presented with a history of bilateral cloudy corneas and tearing since birth. Examination at 3 weeks of age showed bilateral corneal oedema with central corneal opacities, superficial pannus (corneal vascularisation), and iridocorneal adhesions with a well formed anterior chamber (fig 1, above). Iris was present for …