Jean Deschênes

International Uveitis Study Group (IUSG) Clinical Classification of Uveitis

A simplified clinical classification system of uveitis has been proposed by the International Uveitis Study Group. Its aim is to assist in the diagnosis and evaluation of patients with uveitis. Used in conjunction with other recognized classification systems it will also enable enrollment of patients for clinical trials, and contribute to clinical guidelines.

ORIGINAL ARTICLE Visual Outcome of Juvenile Rheumatoid Arthritis-Associated Uveitis in Adults

Purpose: Juvenile rheumatoid arthritis (JRA) is the systemic disease most frequently associated in childhood uveitis. The disease may cause several ocular complications, visual impairment, and blindness. Recent studies revealed a more favorable ocular prognosis. Our purpose was to analyze the long-term visual outcome of JRA-associated uveitis. Methods: Ocular complications and visual outcome in adult patients with JRA-associated uveitis were evaluated. Among 18 patients included in the study, uveitis was bilateral in 12 (66.7%) and unilateral in six (33.3%), for a total of 30 eyes with ocular involvement. Results: The mean durations of JRA and its associated uveitis were 24.9 and 20.5 years, respectively. All eyes (100%) had at least one ocular complication. The most frequently observed ocular complications were cataract (83.3%), band keratopathy (60%), posterior synechia (46.7%), glaucoma (33.3%), hypotony (16.7%), and macular pathology (13.3%). Final visual acuity was impaired in 40% of the eyes, poor in 20%, and totally lost in 10%. Therefore, 70% of the eyes were either visually handicapped or totally blind. Most eyes underwent at least one surgical procedure. Inflammation was active at last examination in 63.3% of eyes. All patients were still treated topically and with systemic NSAID. Sixty-one percent of the patients were using an immunosuppressive agent. Conclusion: JRA-associated uveitis still has a severe course and blinding potential. Patients suffer from uveitis and its complications even during the adulthood period. However, because our series represents a more severe subset of the disease, the outcome may be poorer than that of some other outcome studies.

The VF-14 index of functional visual impairment in candidates for a corneal graft ☆

PURPOSE To validate the Visual Function-14 (VF-14) index of functional visual impairment in candidates for a corneal graft. METHODS One hundred thirty-four patients who were candidates for a corneal graft participated in this study between August 1996 and February 1997. Demographic, ocular history, best-corrected visual acuity, and detailed ocular examination data were collected. Functional visual impairment information was obtained by telephone interviews using the following: VF-14, SF-36 (Short Form-36, a more generic measure of general health function), and Visual Symptom Score, and four questions measuring the overall amount of trouble with vision, dissatisfaction with vision, ocular pain, and discomfort. RESULTS The average age of corneal graft candidates was 64 +/- 18 years (range, 18 to 90 years) and 60% were women. The most frequent corneal disease was pseudophakic bullous keratopathy (41%). Ocular comorbidities included glaucoma or ocular hypertension (30%) and cataract (19%). The mean best-corrected visual acuity of the eye scheduled for surgery was 1.33 +/- 0.56 logMAR whereas the best eye best-corrected visual acuity was 0.36 +/- 0.44 logMAR. The mean VF-14 score was 73% +/- 26%, and the internal consistency was high, with a Cronbach alpha value of 0.94. The VF-14 correlated strongly with the best eye best-corrected visual acuity. It also correlated strongly with the Visual Symptom Score, the global measures of trouble and dissatisfaction with vision. Candidates for a corneal graft had low scores for all eight general health concepts evaluated with the SF-36, and the VF-14 correlated with seven of the eight SF-36 subscales. CONCLUSION The VF-14 is a valid measure of functional visual impairment in candidates for a corneal graft. The Visual Symptom Score and the SF-36 are also useful indices in such patients.

Overexpression of Estrogen Receptors in Columnar Cell Change and in Unfolding Breast Lobules

Abstract:  Columnar cell change (CCC) is common and has often been considered of little clinical interest. However, some investigators have suggested that it may be a marker for increased risk of breast cancer. To see whether CCC is subject to hormonal influences, the distribution of estrogen receptors (ER) was determined in a series of breast specimens showing this change. The cases came from 51 women age 35–80 years (mean 52 years) with the following associated findings: 27 carcinomas and 24 benign lesions. Consecutive sections were recut from the paraffin blocks: one was stained with hematoxylin‐eosin and the other was immunostained for ER. Since CCC is the initial step in unfolding of lobules, a process which can evolve into various conditions, including cyst formation and epithelial hyperplasia, the distribution of ER was also evaluated in the latter conditions. In normal lobules, only a minority of epithelial cells were reactive for ER. In contrast, the cells showing columnar change uniformly expressed strong nuclear reactivity. In lobules undergoing unfolding with the formation of cysts, the lining epithelial cells remained positive even when they became cuboidal or flattened. The pattern of reactivity differs in the two types of hyperplasia. In hyperplasia of the usual type, the pattern was heterogeneous, with a majority of negative cells mixed with cells showing varying degrees of positivity. In columnar cell hyperplasia, the stratified epithelium maintained a strong uniform positivity. It is now recognized that columnar cell lesions include a wide spectrum of changes reaching a point at the upper end where the differential diagnosis is ductal carcinoma in situ. Other studies have shown that advanced CCC lesions with various degrees of hyperplasia and/or atypia are ER positive. The present findings indicate that, from the initial stage of the spectrum, the common columnar cells are strongly ER positive. Moreover, the observation that the lining cells in cysts are positive supports the theory that hormonal factors are involved in the development of fibrocystic changes. 

Determinants of Rifabutin-Associated Uveitis in Patients Treated with Rifabutin, Clarithromycin, and Ethambutol for Mycobacterium avium Complex Bacteremia: A Multivariate Analysis

Uveitis occurred in a substantial proportion of AIDS patients receiving rifabutin, 600 mg daily, together with clarithromycin and ethambutol for treatment of Mycobacterium avium complex bacteremia. A case-control study was undertaken to examine potential risk factors for developing uveitis. Of eight parameters examined, only baseline body weight predicted the development of uveitis by both univariate and multivariate analyses (P = .001). The incidence of uveitis was 14% in patients weighing >65 kg, 45% in patients between 55 and 65 kg, and 64% in patients <55 kg. Concomitant therapy with fluconazole, a drug known to raise serum rifabutin concentrations, was not associated with an increased incidence of uveitis. The risk of uveitis was markedly reduced when rifabutin was given at 300 mg daily in combination with clarithromycin and ethambutol.

Germline truncating mutations in both MSH2 and BRCA2 in a single kindred

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.

The VF-14 index of visual function in recipients of a corneal graft: a 2-year follow-up study.

PURPOSE To assess visual functioning and other health-related quality of life outcomes after corneal grafting. DESIGN A cohort study of corneal graft recipients observed for a minimum of 2 years after transplantation. METHODS Repeated measurements were obtained by telephone interviews preoperatively and later at 1 and 2 years post-corneal transplantation in 217 patients with the following questionnaires: visual function index (VF-14), visual symptom score and global measures of trouble with vision, dissatisfaction with vision, ocular pain, and discomfort. Demographic, past ocular history, repeated best-corrected visual acuity (BCVA), and detailed eye examination data were also collected. RESULTS Grafted eyes gained a mean of more than four lines of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart 1 year after transplantation. The mean visual function index (VF-14) score improved from 68% +/- 26% preoperatively to 81% +/- 21% at 1 year. Average visual acuity (VA) and VF-14 values were unchanged at 2 years. The activities of daily living that showed the largest and most significant improvement were reading small print, driving in daytime, and watching television. A number of subjects (9%) presented with a maximum VF-14 score preoperatively, leaving no room for improvement with this outcome index. The VF-14 was especially responsive for corneal graft candidates with low levels of vision before surgery. Blurry vision, pain and discomfort scores, and the global measures of trouble and dissatisfaction with vision also improved after corneal grafting. CONCLUSION The VF-14 index of functional visual impairment is a responsive and useful outcome index in recipients of a corneal graft.

Zidovudine-Induced Macular Edema

Zidovudine has become the standard therapy for patients with altered immunity due to infection with human immunodeficiency virus (HIV). Initially, the drug was studied in patients who were in the a...

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20‐month period. One hundred and ninety‐two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9–7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1–53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (≤20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site‐specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.

Ultrasound biomicroscopy of pseudophakic eyes with chronic postoperative inflammation

Purpose: To evaluate the ultrasound biomicroscopy (UBM) findings in pseudophakic eyes with chronic noninfectious postoperative inflammation and discuss the use of the technique in these cases. Setting: Uveitis Service, Department of Ophthalmology, McGill University, Montréal, Québec, Canada. Methods: Fifty‐four eyes of 51 patients with chronic noninfectious postoperative inflammation were prospectively evaluated between January 1998 and September 2001. Patients with aphakia, a dislocated intraocular lens (IOL) in the posterior segment, and endophthalmitis were excluded. All patients had a UBM examination that comprised locating the IOL position, investigating the presence of lens remnants, and evaluating the anterior segment of the eye. Results: Ultrasound biomicroscopic examination revealed IOL misplacement in 37 eyes (68.5%). Of these, 23 (62.2%) had a sulcus‐implanted posterior chamber IOL (PC IOL), 9 (24.3%) an in‐the‐bag PC IOL, and 5 (13.5%) an anterior chamber IOL. Haptic misplacement was significantly higher with sulcus‐implanted PC IOLs than with in‐the‐bag PC IOLs (P<.01). Other UBM findings included edematous ciliary body processes and hypoechogenic and/or thickened ciliary bodies in 11 eyes (20.4%), peripheral anterior synechias in 8 eyes (14.8%), a significant number of lens remnants (graded as severe) in 6 eyes (11.1%), a thick cyclitic membrane in 3 eyes (5.6%), and an early cyclitic membrane in 2 eyes (3.7%). Conclusions: Irritation of ocular tissues by an IOL was the main cause of chronic postoperative noninfectious inflammation in pseudophakic eyes. Therefore, detecting the IOL position and its relationships to ocular tissues is very important in planning the treatment. Ultrasound biomicroscopy is a practical method that accurately provides this information.