High concordance of intraocular antibody synthesis against the rubella virus and Fuchs heterochromic uveitis syndrome in Slovenia.

PURPOSE: To prospectively study the relationship between Fuchs heterochromic uveitis syndrome (FHUS) and intraocular production of specific antibodies against the rubella virus (RV) in Slovenia. METHODS: Using the Goldmann-Witmer coefficient technique, intraocular synthesis of specific antibodies against RV, herpes simplex virus, varicella-zoster virus, cytomegalovirus (CMV) and Toxoplasma gondii-specific immunoglobulin G antibodies was performed in 12 consecutive patients with clinically diagnosed FHUS and 12 patients with idiopathic recurrent unilateral anterior uveitis (AU) without clinical features of FHUS. RESULTS: Specific intraocular antibody synthesis against RV with a positive Goldmann-Witmer coefficient was proven in 11 of 12 (92%) FHUS patients, and in none of the non-FHUS AU patients (Fisher's exact test <0.0001). In one patient with FHUS, specific antibodies against RV and varicella-zoster virus were concurrently detected. Specific antibodies against cytomegalovirus were detected in one patient with unilateral recurrent AU. CONCLUSIONS: Intraocular production of specific immunoglobulin G against RV was proven in the majority of tested cohort of FHUS patients from Slovenia as compared to the group of patients with idiopathic AU, which suggests that RV is involved in the pathogenesis of FHUS in this geographic area.

Ultrastructure of the anterior lens capsule and epithelium in cataracts associated with uveitis.

AIMS: To study the ultrastructure of the anterior lens capsule and epithelium, and capsular thickness in uveitic cataracts. METHODS: Capsulorhexis samples from 20 uveitic cataracts were compared to 20 nuclear cataracts using the semi- and ultra-thin techniques. RESULTS: Extensive epithelial and capsular-epithelial border changes and epithelial-mesenchymal transition in some fibrotic capsules were found only in the uveitic group. All these changes were observed predominately in white uveitic cataracts. Mild and moderate ultrastructural changes were seen in both groups. Surface deposition of amorphous material was also found only in uveitic cataracts. Capsular thickness was not different between the two groups. CONCLUSIONS: Uveitic capsules showed more extensive and different ultrastructural changes that probably occurred because of inflammation in the eye and epithelial-mesenchymal transition. These changes might be an additional reason for altered behavior of the lens capsule at capsulorhexis.

Intraocular and serum cytokine profiles in patients with intermediate uveitis.

PURPOSE: To study the intraocular and serum cytokine and chemokine profile in patients with intermediate uveitis (IU) at various stages of inflammatory activity. METHODS: Institutional, prospective association study. Paired aqueous humor (AqH) and serum samples were collected from 36 consecutive IU patients and 10 controls. The concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF)-α, CC--chemokine ligand 5/regulated upon activation normal T-cell expressed, and secreted (CCL5/RANTES), CC--chemokine ligand 3/macrophage inflammatory protein 1alpha (CCL3/MIP-1α), CCL4/MIP-1ß, and CC--chemokine ligand 2/monocyte chemotactic protein--1 (CCL2/MCP-1) were measured in both AqH and serum by multiplex immunoassay. Main outcome measures were serum and intraocular levels of the analyzed cyto- and chemokines. RESULTS: Patients with IU had higher serum levels of TNF-α than non-uveitic controls (p<0.0001), whereas their AqH TNF-α levels did not show a difference (p=0.323). IU patients had higher intraocular levels of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and CCL2/MCP-1 than the controls (p=0.020, 0.001, <0.0001, 0.005, 0.003, and 0.003, respectively). Active stages of IU were characterized by higher levels of IL-6, IL-8, CCL5/RANTES and CCL2/MCP-1 (p=0.003, <0.0001, 0.033, and 0.033, respectively). Higher levels of IL-6 and IL-8 were found in IU patients with cystoid macular edema (CME) compared to non-CME IU patients (p=0.026 and 0.012, respectively). Significant positive correlations between various observed mediators were present in the AqH of IU patients only. CONCLUSIONS: Significantly elevated concentrations of multiple intraocular cytokines were found in IU patients, especially IL-6 and IL-8 in those with CME and active disease. In serum elevated TNF-α levels were observed in IU patients. Our findings improve the understanding of the pathogenesis of IU and contribute to the identification of factors which may contribute to the activity of IU.

Efficacy of 12-month treatment of neovascular age-related macular degeneration with intravitreal bevacizumab based on individually determined injection strategies after three consecutive monthly injections.

PURPOSE: To report the results of intravitreal treatment with bevacizumab in neovascular age-related macular degeneration (AMD) after a loading dose (LD) of three monthly injections followed by an optical coherence tomography (OCT)-guided strategy, based on best-corrected visual acuity (VA) and number of injections required over 1 year. METHODS: A series of consecutive cases of 149 eyes of 147 patients received three or more intravitreal injections of bevacizumab (1.25 mg) for neovascular AMD over a 1-year period. The patients underwent ophthalmological examinations: measurement of the VA, fluorescein angiography, dilated fundus examination at baseline; VA, OCT and dilated fundus examination at monthly follow-up visits. Repeated injections were given each month for the first 3 months (LD); thereafter, injections were only administered if leakage or macular oedema were present. RESULTS: Mean baseline VA was 51 ± 14 letters, which improved to 58 ± 15 letters (p < 0.0001; n = 149) at first evaluation (15 ± 2 weeks), 59 ± 15 letters (p < 0.0001; n = 143) at second evaluation (25 ± 2 weeks) and 57 ± 16 letters (p < 0.0001; n = 132) at third evaluation (51 ± 3 weeks). The baseline mean central retinal thickness (344.6 µm) and total macular volume (8.6 mm(3) ) decreased at first evaluation, to 219.0 µm (p < 0.0001) and 7.2 mm(3) (p < 0.0001), respectively. The mean number of injections per patient treated for 1 year was 5.1 (range 3-9). No systemic side-effects were noted. CONCLUSION: Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of three monthly injections and followed by an OCT-guided strategy provides functional and anatomical improvements for up to 1 year.

Effect of tinted optical filters on visual acuity and contrast sensitivity in patients with inflammatory cystoid macular edema.

PURPOSE: To ascertain the effect of tinted optical filters (TFs) on visual function in patients with inflammatory cystoid macular edema (CME). METHODS: A prospective study included 14 patients with inflammatory CME and best-corrected visual acuity between 0.1 and 0.8 (CME group) and 16 sex-, age-, and best-corrected visual acuity-matched patients with macular disorders but no CME (non-CME group). All patients from both groups underwent the following tests: determination of visual acuity at distance, contrast sensitivity (CS) testing; and subjective grading of each TF for best-corrected visual acuity and CS compared with no TFs. All tests were performed with the following TFs: Corning photochromic filter with a cutoff at 450 nm; Zeiss filter with a cutoff at 560 nm; and cheap widely available yellow filter with a cutoff at 489 nm. RESULTS: Without TFs, the CME and non-CME groups did not differ in best-corrected visual acuity (P = 0.79). Using the TFs, a clinically significant improvement was not achieved by any patient. However, using the definition of any improvement, best-corrected visual acuity with all TFs showed a significant improvement in the CME group compared with no TFs (P < 0.01). The CME group rated the Corning photochromic filter with a cutoff of 450 nm significantly higher than the other TFs when determining visual acuity (P = 0.05) and CS (P = 0.01) in contrast to no improvement in the non-CME group. CONCLUSION: Although the use of TFs for the CME patients was not associated with criteria of clinically significant improvement, our results indicate that visual acuity and CS in patients with inflammatory CME might benefit from the use of TFs.

Vitreous hemorrhage in multiple sclerosis-associated uveitis.

PURPOSE: To report on six patients who developed vitreous hemorrhage (VH) in the course of intermediate uveitis (IU) associated with multiple sclerosis (MS). METHODS: Observational case series. RESULTS: Six out of 25 patients (24%) with IU and MS seen at two tertiary centers developed VH. Average age at onset of MS was 26 years and average age at the onset of IU was 25 years. IU developed before the onset of MS in four of the six patients (67%). All patients had IU associated with peripheral phlebitis. The average interval between the onset of IU and the occurrence of VH was five years (range: 0-11 years; VH was the initial sign of uveitis in 2 patients). VH cleared spontaneously in all cases; however, subsequent retinal detachment developed in two eyes. All six patients had ischemic retinal areas and four had subretinal neovascularizations. Optimal visual acuity five years after VH varied from no light perception to full visual acuity. The causes of diminished acuity included optic neuritis, cystoid macular edema (CME), and retinal detachment. CONCLUSION: The possibility of MS-associated uveitis should be considered in patients with IU and VH.

Seroprevalence of Toxocara antibodies among patients suspected of ocular toxocariasis in Slovenia.

Ocular toxocariasis named also ocular larva migrans is caused by larvae of the roundworm Toxocara spp. The purpose of this study was to find out the seroprevalence of Toxocara antibodies in patients suspected of ocular toxocariasis. Between January 2001 and December 2003, sera from 239 ocular patients, aged 3 to 80 years, were examined by ELISA and confirmed by Western blot test. Out of the 239 patients, 172 (72%) were seronegative and 67 (28%) were Toxocara seropositive; 95% CI (22-34%). The median age of Toxocara seropositive patients was 37.6 years. There was no significant difference in the number of Toxocara positive sera between the younger age group (< or = 14 years) and the older age group (> 14 years), p > 0.05. A high rate of Toxocara seropositivity in ocular patients should alert the ophthalmologists in Slovenia to include toxocariasis in the differential diagnosis of eye diseases more frequently.

Fundus autofluorescence imaging in Best's vitelliform dystrophy.

BACKGROUND: It is well known that with age lipofuscin accumulates in the retinal pigment epithelium (RPE). In many inherited macular dystrophies such as Best's disease abnormally high levels of lipofuscin were found by histopathological studies. In recent years, it has become possible to detect and image fundus autofluorescence in the living eye as an index of lipofuscin accumulation in the RPE. The aim of our study was to document the intrinsic fundus autofluorescence in patients with different stages of Best's disease and to correlate fundoscopic features with visual function in these patients. METHODS: Images of fundus autofluorescence were obtained from 10 patients with Best's vitelliform dystrophy, using a Heidelberg Retina Angiograph (HRA). Argon laser light (488 nm) was used for illumination, and a wide-bandpass filter with a cutoff of 500 nm was inserted in front of the detector to obtain the autofluorescence images. Images were compared with fundus appearance and fluorescein angiograms as well as with visual acuity, colour vision, visual fields and electrophysiological recordings in these patients. RESULTS: In initial stages of Best's disease, there were localised areas of hyperfluorescence centrally in the fovea, later being replaced by central hypofluorescence (atrophic) areas surrounded by hyperfluorescent rings. The evolution of autofluorescence pattern showed centrifugal spreading of retinal dysfunction from the centre towards periphery. Atrophic regions of the RPE were associated with low levels of background autofluorescence, lower visual acuity, abnormal colour vision (70% of patients), central scotomas (85% of patients) and poorer electrophysiological results (reduced PERG responses in 45% of patients with Best's disease). CONCLUSIONS: Fundus autofluorescence imaging provides new information regarding the content and spatial distribution of RPE lipofuscin in eyes with Best's disease, which appears to correspond to retinal function. This may "in vivo" give important clues to the pathogenesis and progression of Best's disease in which non-invasive autofluorescence imaging may replace fluorescein angiography.

Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women.

A programme for the prevention of congenital toxoplasmosis in Slovenia involving the screening of pregnant women for Toxoplasma infection is presented. Of 21,270 pregnant women screened for toxoplasmosis between, 1996 and the end of 1999, 13,987 (66%) were seronegative, 7,151 (34%) seropositive and 132 had primary infection; approximately 9/1,000 women were at risk of acquiring the primary infection. One hundred live-born infants of primary infected women were available for follow-up. Nine infected but asymptomatic children were born to mothers who were screened and treated in time and two congenitally infected babies were born to mothers in whom infection was detected too late in pregnancy and who therefore received no adequate treatment. It is suggested that the results obtained in this study outweigh the cost of screening for toxoplasmosis in pregnancy. Pregnant women should always be tested at the beginning of pregnancy and, in cases of seronegativity, should be re-tested in the second and third trimesters of the pregnancy. Toxoplasma primary infected pregnant women and neonates should be treated as soon as possible. However, long-term follow-up of children born to primary infected women would be necessary for an accurate evaluation of the effectiveness of the screening because of the possibility of late onset of symptoms.