Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment.

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood-retinal and blood-brain barriers for patients with GD and other neuropathic lysosomal storage disorders.

Six-year prevalence and incidence of diabetic retinopathy and cost-effectiveness of tele-ophthalmology in Manitoba.

OBJECTIVE: The purpose of this study was to evaluate the diabetic retinopathy (DR) tele-ophthalmology screening program in Manitoba to determine prevalence and incidence of DR, as well as to estimate the program's cost-effectiveness. DESIGN: Retrospective chart review. PARTICIPANTS: A total of 4676 patients with type 2 diabetes examined 9334 times from 2007 to 2013. METHODS: Focused ophthalmic histories were recorded and examinations were performed by trained nurses, including visual acuities, intraocular pressure, and mydriatic 7 standard field stereoscopic fundus photography. Images were evaluated by retinal specialists according to the Early Treatment of Diabetic Retinopathy Study criteria. DR prevalence and incidence were then calculated during the study period. Cost-effectiveness was estimated by comparing the cost of running the tele-ophthalmology program compared with the cost of screening the same volume of patients in-office. RESULTS: The average prevalence of any DR in each year was 25.1%. The cumulative incidence of DR across 6 years was 17.1% (95% CI, 15.4%-18.7%). The average savings per tele-ophthalmology examination was $1007. CONCLUSIONS: DR is highly prevalent among the studied population. Tele-ophthalmology provides a cost-effective means of monitoring patients as well as identifying new or treatable disease.

Six-year prevalence and incidence of diabetic retinopathy and cost-effectiveness of tele-ophthalmology in Manitoba.

OBJECTIVE: The purpose of this study was to evaluate the diabetic retinopathy (DR) tele-ophthalmology screening program in Manitoba to determine prevalence and incidence of DR, as well as to estimate the program's cost-effectiveness. DESIGN: Retrospective chart review. PARTICIPANTS: A total of 4676 patients with type 2 diabetes examined 9334 times from 2007 to 2013. METHODS: Focused ophthalmic histories were recorded and examinations were performed by trained nurses, including visual acuities, intraocular pressure, and mydriatic 7 standard field stereoscopic fundus photography. Images were evaluated by retinal specialists according to the Early Treatment of Diabetic Retinopathy Study criteria. DR prevalence and incidence were then calculated during the study period. Cost-effectiveness was estimated by comparing the cost of running the tele-ophthalmology program compared with the cost of screening the same volume of patients in-office. RESULTS: The average prevalence of any DR in each year was 25.1%. The cumulative incidence of DR across 6 years was 17.1% (95% CI, 15.4%-18.7%). The average savings per tele-ophthalmology examination was $1007. CONCLUSIONS: DR is highly prevalent among the studied population. Tele-ophthalmology provides a cost-effective means of monitoring patients as well as identifying new or treatable disease.

Stress Doppler echocardiography for early detection of systemic sclerosis-associated pulmonary arterial hypertension.

INTRODUCTION: In patients with systemic sclerosis (SSc), associated pulmonary arterial hypertension (SSc-APAH) is the leading cause of death. The objective of this prospective screening study was to analyse sensitivity and specificity of stress Doppler echocardiography (SDE) in detecting pulmonary hypertension (PH). METHODS: Pulmonary artery pressures and further parameters of PH were assessed by echocardiography and right heart catheterisation (RHC) at rest and during exercise in patients with SSc. Investigators of RHC were blinded to the results of non-invasive measurements. RESULTS: Of 76 patients with SSc (64 were female and mean age was 58±14 years), 22 (29 %) had manifest PH confirmed by RHC: four had concomitant left heart diseases, three had lung diseases, and 15 had SSc-APAH. Echocardiography at rest missed PH diagnosis in five of 22 patients with PH when a cutoff value for systolic pulmonary arterial pressure (PASP) was more than 40 mm Hg at rest. The sensitivity of echocardiography at rest was 72.7 % (95 % confidence interval (CI) 0.52-0.88), and specificity was 88.2 % (95 % CI 0.78-0.95). When a cutoff value for PASP was more than 45 mm Hg during low-dose exercise, SDE missed PH diagnosis in one of the 22 patients with PH and improved sensitivity to 95.2 % (95 % CI 0.81-1.0) but reduced specificity to 84.9 % (95 % CI 0.74-0.93). Reduction of specificity was partly due to concomitant left heart disease. CONCLUSIONS: The results of this prospective cross-sectional study using RHC as gold standard in all patients showed that SDE markedly improved sensitivity in detecting manifest PH to 95.2 % compared with 72.7 % using echocardiography at rest only. Thus, for PH screening in patients with SSc, echocardiography should be performed at rest and during exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT01387035. Registered 29 June 2011.

Exercise training in pulmonary arterial hypertension associated with connective tissue diseases.

INTRODUCTION: The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). METHODS: Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. RESULTS: Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. CONCLUSION: ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00491309.

Teleophthalmology screening for diabetic retinopathy through mobile imaging units within Canada.

BACKGROUND: This study aimed to describe and measure the health results of a Category 3 teleophthalmology screening project for diabetic retinopathy (DR). Implemented through mobile screening imaging units located within pharmacies, the project had the goal of reaching unscreened diabetic patients in urban communities while lowering barriers to screening and saving medical resources. METHODS: Image capture of both eyes of 3505 known diabetic individuals was performed in the provinces of Quebec, British Columbia, Alberta, Manitoba, and Saskatchewan. A photographer performed fundus imaging, and a nurse used mild pupil dilation only when necessary to secure image quality. Screening was provided free of cost in the context of DR health days for DR screening. Through teleophthalmology, ophthalmologists proceeded with data and image interpretation, and timely referral when indicated. RESULTS: This project allowed the resumption of screening of over 38% of the cohort of known diabetics who reported never having undergone any eye examination with pupil dilation, and an additional 30% who reported not having been examined for over 2 years. All known diabetics were under the care of a general physician, and their mean diabetes duration, when known, was 8 years. DR pathology was found in 22.5% (20%-28%) of the cohort, 1.8% requiring urgent referral (within 30 days) as a result of the severity of the DR and 0.6% (0%-1.8%) requiring urgent referral for other reasons. An additional 8.7% (8.1%-19.5%) required ophthalmologic attention within 6 months because of DR and another 2.0% (0%-6.3%) between 6 months and 1 year. Incidental findings were found in 23%, the majority of which were related to cataract and dry macular degeneration. Urgent or significant incidental findings were found in 0.6% of the screened eyes. Pupil dilation with tropicamide 1% was deemed useful or necessary in 33.7% of the cohort. For 0.7% of the cohort, the images could not be interpreted because of poor image quality and for that reason had to be referred for a traditional dilated eye examination. Ophthalmologists were relieved of the examination of 85.6% of the screened diabetic individuals who benefited from screening without requiring a traditional ophthalmologic examination. On the other hand, ophthalmologists were required to provide urgent (within 30 days) services to 2% of the cohort, either because of threatening DR or because of incidental findings requiring rapid ophthalmologic attention. INTERPRETATION: This screening strategy for DR through mobile teleophthalmology imaging units efficiently lowered barriers to screening and created new screening opportunities for a large number of known diabetic individuals who were lost to the traditional health system. It has the potential to provide better outreach to diabetic populations while identifying individuals truly in need of the services of an ophthalmologist; at the same time it maximizes the use of limited ophthalmologic resources while favouring multidisciplinary collaborations. The significant incidental findings associated with screening highlight the need for ophthalmologic competencies during DR screening within a teleophthalmology approach. Further involvement of government health authorities is pivotal in embracing the opportunities provided by emerging technologies such as teleophthalmology and translating them into better outreach services to diabetic populations and thus better visual health results.

A picture worth remembering: posttraumatic Purtscher's retinopathy in a child.

Purtscher's retinopathy is frequently described and reviewed in the ophthalmology literature but is rarely described in the neurology literature, although neurologists are routinely involved in the care of head and chest trauma patients with abnormal neurologic and funduscopic findings. The case of a 6-year-old girl with Purtscher's retinopathy is described, and the relevant literature is reviewed.

West Nile chorioretinitis.

CASE REPORT: The clinical course of 2 Canadian cases of West Nile chorioretinitis is described. The patients developed visual-field disturbances shortly after flu-like illnesses and were referred for retinal evaluation. Full ophthalmologic examination included Snellen visual acuity testing, applanation tonometry, slit-lamp examination, dilated fundus examination, fundus photography, and fluorescein angiography. Both patients developed self-limited cases of chorioretinitis exhibiting characteristic fundus and fluorescein angiographic findings. COMMENTS: Since the introduction of West Nile virus to Canada and its progressive spread across the country, more patients will present to their eye specialists with chorioretinitis. In cases of chorioretinal inflammation, West Nile virus infection should be included in the differential diagnosis.