Evaluation of corneal endothelium and keratic precipitates by specular microscopy in anterior uveitis

Background - The study of corneal endothelium, by specular microscopy, in patients with anterior uveitis has largely been restricted to observations on the endothelial cells. In this prospective study 'keratic precipitates' (KP) in different types of uveitis were examined in different stages of the disease process and the endothelial changes occurring in the vicinity of the KP were evaluated in comparison with the endothelium of the uninvolved eye. Methods - 13 patients with active unilateral uveitis were recruited. The mean age was 42.9 years (range 20-76 years). A Tomey-1100 contact wide field specular (x10) microscope was used to capture endothelial images and KP until the resolution of uveitis. Data regarding type of uveitis, number, size, and nature of KP were recorded. Automated morphometric analysis was done for cell size, cell density and coefficient of variation, and statistical comparisons of cell size and cell density were made (Student's t test) between the endothelium in the vicinity of fresh and resolving KP, fresh KP and normal endothelium, and resolving KP and normal endothelium. Results - On specular microscopy, fresh KP were seen as dense, white glistening deposits occupying 5-10 endothelial cells in diameter and fine KP were widely distributed and were one or two endothelial cells in diameter. The KP in Posner-Schlossman syndrome had a distinct and different morphology. With clinical remission of uveitis, the KP were observed to undergo characteristic morphological changes and old KP demonstrated a large, dark halo surrounding a central white deposit and occasionally a dark shadow or a 'lacuna' replaced the site of the original KP. Endothelial blebs were noted as dark shadows or defects in the endothelial mosaic in patients with recurrent uveitis. There was significant statistical difference in the mean cell size and cell density of endothelial cells in the vicinity of fresh KP compared with normal endothelium of the opposite eye. Conclusion - This study elucidated the different specular microscopic features of KP in anterior uveitis. Distinct morphological features of large and fine KP were noted. These features underwent dramatic changes on resolution of uveitis. The endothelium was abnormal in the vicinity of KP, which returned to near normal values on resolution of uveitis.

Successful medical treatment of Acanthamoeba keratitis

Purpose: To describe the outcome of a series of Acanthamoeba keratitis treated with a similar regimen. Methods: All cases diagnosed with Acanthamoeba keratitis in a referral centre from June 1994 through June 1997 were included. Diagnosis of Acanthamoeba keratitis was based in clinical presentation and laboratory results. Positive laboratory identification of Acanthamoeba from corneal scraping or contact lens was required, unless the patient had very characteristic symptoms (severe pain) and signs of the infection, including perineural infiltrates. Initial intensive treatment included topical polyhexamethylene biguanide (PHMB) 0.02%, propamidine isothionate 0.1% and broad-spectrum antibiotics. The treatment was gradually tapered. After documented response to anti-acanthamoeba therapy, topical steroids were introduced; they were discontinued before cessation of the antiAcanthamoeba regimen. Results: Six males and four females, with a mean age of 30.0 ± 7.4 years were included in this study. All cases weared contact lenses. On presentation all cases had severe pain, and epitheliopathy was associated with stromal infiltrate in most (seven of ten) cases. Four patients had anterior uveitis. Perineural infiltrates were present in three cases and ring infiltrate in one patient. Anti-amoebic treatment was started 12.7 ± 7.2 days after beginning of symptoms. The clinical response to therapy was very satisfactory in all patients. Within two to three weeks all patients had remarkable lessening of pain and photophobia, and improvement of clinical signs. At two to three months, visual acuity had improved in all patients. Two patients required penetrating keratoplasty for visual rehabilitation. Conclusion: The use of PHMB and propamidine cured all cases of Acanthamoeba keratitis. Cautious introduction of steroids was associated with expedited resolution of inflammation and provided symptomatic relief.

Incidence of glaucoma in patients with uveitis

Purpose: To evaluate the incidence of glaucoma and elevation of intraocular pressure (IOP) in patients with inflammatory eye disease. Methods: Retrospective review of medical records of 391 consecutive patients with uveitis attending a uveitis clinic of an academic Department of Ophthalmology from January 1999 to August 2002. Demographic, ocular and systemic variables were recorded. The diagnosis and treatment of uveitis were recorded. Uveitis was classified according to standard anatomic, etiological and clinical criteria. "Glaucoma" was defined as elevated IOP (>21 mm Hg) or glaucomatous optic nerve damage requiring medical and/or surgical anti-glaucoma treatment. Kaplan-Maier analysis and log-rank tests were used to evaluate and compare the incidence of glaucoma. Results: The incidence of glaucoma as defined above at 3 and 12 months after acute uveitis was 7.6%. In patients with chronic uveitis (n = 337), the incidence of glaucoma at 1 and 5 years was 6.5% and 11.1%, respectively. There was no statistically significant difference in the incidence of glaucoma between different types of uveitis, idiopathic versus non-idiopathic, and among anterior, intermediate, posterior and panuveitis. Visual loss occurred more frequently in patients with glaucoma than in patients without glaucoma. Conclusion: In patients with chronic inflammatory eye disease, the presence of glaucoma was associated with an increasing risk of visual loss. The incidence of glaucoma increased with time and was similar among the different types of uveitis.

Anterior thalmic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats

Lesions involving the anterior thalamic nuclei stopped immediate early gene (IEG) activity in specific regions of the rat retrosplenial cortex, even though there were no apparent cytoarchitectonic changes. Discrete anterior thalamic lesions were made either by excitotoxin (Experiment 1) or radiofrequency (Experiment 2) and, following recovery, the rats foraged in a radial-arm maze in a novel room. Measurements made 6-12 weeks postsurgery showed that, in comparison with surgical controls, the thalamic lesions produced the same, selective patterns of Fos changes irrespective of method. Granular (caudal granular cortex and rostral granular cortex), but not dysgranular (dysgranular cortex), retrosplenial cortex showed a striking loss of Fos-positive cells. While a loss of between 79 and 89% of Fos-positive cells was found in the superficial laminae, the deeper layers appeared normal. In Experiments 3 and 4, rats 9-10 months postsurgery were placed in an activity box for 30 min. Anterior thalamic lesions (Experiment 3) led to a pronounced IEG decrease of both Fos and zif268 throughout the retrosplenial cortex that now included the dysgranular area. These IEG losses were found even though the same regions appeared normal using standard histological techniques. Lesions of the postrhinal cortex (Experiment 4) did not bring about a loss of retrosplenial IEG activity even though this region is also reciprocally connected with the retrosplenial cortex. This selective effect of anterior thalamic damage upon retrosplenial activity may both amplify the disruptive effects of anterior thalamic lesions and help to explain the posterior cingulate hypoactivity found in Alzheimer's disease.

Changes in fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.

Fos imaging reveals that lesions of the anterior thalamic nuclei produce widespread limbic hypoactivity in rats

Activity of the immediate early gene c-fos was compared in rats with neurotoxic lesions of the anterior thalamic nuclei and in surgical controls. Fos levels were measured after rats had been placed in a novel room and allowed to run up and down preselected arms of a radial maze. An additional control group showed that in normal rats, this exposure to a novel room leads to a Fos increase in a number of structures, including the anterior thalamic nuclei and hippocampus. In contrast, rats with anterior thalamic lesions were found to have significantly less Fos-positive cells in an array of sites, including the hippocampus (dorsal and ventral), retrosplenial cortex, anterior cingulate cortex, and prelimbic cortex. These results show that anterior thalamic lesions disrupt multiple limbic brain regions, producing hypoactivity in sites associated in rats with spatial memory. Because many of the same sites are implicated in memory processes in humans (e.g., the hippocampus and retrosplenial cortex), this hypoactivity might contribute to diencephalic amnesia.