[Monitoring treatment with biologics in non-infectious uveitis]. / Monitoring bei Biologikatherapie der nichtinfektiösen Uveitis.

Biologics are increasingly being used in the treatment of non-infectious sight-threatening uveitis. While the advantages of biologics, such as avoidance of glucocorticoid side-effects or rapid control of intraocular inflammation therapy refractive to corticosteroids, cannot be dismissed the treating ophthalmologist should be aware of the specific risks. Biologics increase the risk for severe and atypical infections, lymphomas and other malignancies. Treatment should only be initiated when profound knowledge about indications, management and monitoring of treatment with biologics is readily available. Weighing up the risks versus the benefits should be made on an individual basis and guide patient consultation.

Distress, depression and coping in HLA-B27-associated anterior uveitis with focus on gender differences.

BACKGROUND/AIMS: To evaluate depression, coping with disease and stress, and the subjective impression of distress and/or life events as triggers for recurrences in HLA-B27-associated anterior uveitis (B27-AU), with attention to gender-specific characteristics. METHODS: 171 patients with a history of B27-AU responded to a postal survey performed between January 2006 and April 2008 using standardised psychological questionnaires: Beck Depression Inventory, Freiburg Questionnaire on Coping with Illness, and Stress Coping Inventory. RESULTS: Patients with B27-AU differed from healthy controls showing more depressive symptoms (Beck Depression Inventory, 31.6%), applying characteristic disease coping as well as negative stress coping strategies. Female B27-AU patients tended to react with depression and male patients to use negative stress coping strategies. 57.9% of patients believed that psychological distress was a trigger for relapses, and 34.5% stated specific life events. Together, this group of patients achieved higher depression scores and used more negative disease and stress coping styles than patients without perception of distress. CONCLUSION: Patients with B27-AU patients exhibited significant psychopathology concerning depression and disease coping. Distress and life events were subjectively suspected to be a trigger. By imparting knowledge to the patients on probable development of depressive moods and the role of stress/life events as trigger for relapses, as well as offering behaviour therapy to optimise coping, may help patients to cope better with B27-AU.

Central visual field impairment during and following cystoid macular oedema.

AIM: To determine differential light threshold values obtained with the Micro Perimeter 1 (MP1) in uveitis patients suffering from cystoid macular oedema (CMO) and to compare these measures to retinal thickness. METHODS: Static threshold perimetry was performed with the MP1 Microperimeter in 27 eyes of 21 patients with a history of chronically recurring CMO. Active CMO was confirmed in 19 eyes. Eight eyes with a history of recurrent CMO were found to have normal foveal contours in optical coherence tomography (OCT). Differential light threshold values (MP1) were compared with the corresponding retinal thickness measures (OCT). RESULTS: Mean differential threshold values within the central two degrees of the stimulation pattern were reduced compared with normal values and ranged from 5.8 to 9.5 dB in CMO eyes and from 9.3 to 12.9 dB in eyes with a normal foveal contour but a history of previous CMO. The corresponding mean retinal thickness ranged from 390 (SD 90) to 389 (88) microm (at 0 degrees and 1 degree, respectively) for active CMO and from 199 (36) to 211 (33) microm in eyes with normal fovea following CMO resolution. Statistical correlations between mean differential sensitivity threshold and retinal thickness were only weak and showed no association. CONCLUSIONS: Active CMO causes a marked reduction in central retinal sensitivity. In addition, following the resolution of the CMO, a substantial impairment of central retinal sensitivity remains. Morphology in terms of retinal thickness in OCT does not correlate with visual function in terms of retinal sensitivity in these patients.

Cytomegalovirus antibodies in tear fluid of patients with retinitis.

The diagnosis of cytomegalovirus retinitis (CMV-R) is difficult and usually based on clinical criteria or invasive diagnostic procedures. The purpose of this study was to investigate a possible association between CMV-R and specific anti-CMV antibodies in tears. Paired tear and serum samples were obtained from 96 individuals, which included 20 children with congenital CMV infection and chorioretinitis, 56 adults with retinitis with clinical signs suggestive of viral infection, and 20 healthy control subjects, and were tested for CMV antibodies using ELISA. The prevalence of anti-CMV antibodies in tears was found to be 80% (16/20) in children, 35% (20/56) in adults, and 5% (1/20) in control subjects. Furthermore, high antibody levels were detected in 35% (7/20) of children and 10.7% (6/56) of adults with retinitis, and were not found in control subjects. There was a strong association between high tear levels of anti-CMV antibodies and active ocular infection. No correlations were found between tear and serum antibodies. ELISA sensitivity was 80% and specificity 95%. Further studies are needed to compare the tear and intraocular levels of CMV-specific antibodies in patients with retinitis to find out if CMV antibody testing in tear fluid could substitute for more invasive diagnostic procedures.

Interferon as a treatment for uveitis associated with multiple sclerosis.

AIM: In addition to optic neuritis (ON), multiple sclerosis (MS) may also involve the eye with a typically bilateral intermediate uveitis. The aim of this pilot study was to evaluate the efficacy of type I interferons (IFN) for the treatment of MS associated uveitis. METHODS: In this non-randomised, retrospective observational case series 13 patients (eight female, five male) with proved MS and associated uveitis from five uveitis centres who were treated with interferon beta1a were included. Visual acuity (VA), cell count in the aqueous humour and vitreous, as well as the presence of cystoid macula oedema (CMO) were observed. RESULTS: All except one patient had a bilateral form of intermediate uveitis (total of 24 eyes). Seven patients had documented CMO before IFN treatment (n = 13 eyes). Median duration of treatment was 24.6 months (range 7.9-78.7). VA improved in 17 eyes (comparing VA before therapy and at last follow up); while 10 eyes (36%) improved >or=3 Snellen lines. Aqueous cell count improved by 1.2 (SD 1.1) grades in all eyes. Vitreous cell count improved by 1.7 (1.4) in all eyes. Only two patients still had minimal CMO on last follow up angiographically. CMO resolved after or during IFN treatment in nine eyes. CONCLUSIONS: IFN has been shown to have beneficial effects in patients with MS and/or ON. As shown in the models of experimental allergic encephalomyelitis (EAE) and uveitis, the neurological and ophthalmological manifestations seem to share similar pathogenic mechanisms. Treatment of MS associated uveitis with IFN appears to have beneficial effects on VA, intraocular inflammation activity, and the presence of CMO.

Semicircular tumor of the iris and uveitis as unilocal manifestation of sarcoidosis.

PURPOSE: To describe an unusual manifestation of sarcoidosis as a large tumor of the iris and ciliary body without any other involvement of the body. METHODS: We describe a 20-year-old female presenting with a granulomatous tumor of the right iris and ciliary body and concomitant uveitis. RESULTS: Extensive ocular and systemic workup revealed the tumor to be a large solitary sarcoid granuloma. As systemic steroids were not able to control the activity of the uveitis and granuloma, only the initiation of immunosuppressive therapy with cyclosporine A achieved a lasting remission. CONCLUSION: The possibility of an exclusively ocular sarcoidosis should always be kept in mind despite negative regular screening tests. In these cases, a biopsy should be considered and immunosuppressive agents like cyclosporine A should be evaluated in cases not responding to first-line treatment with systemic steroids.

Treatment of ocular toxocariasis with albendazole.

The purpose of this study was to evaluate the efficacy of combined albendazole and steroid treatment for uveitis caused by Toxocara canis in immunocompetent patients. Five patients (7 eyes) with ocular larva migrans syndrome (OLM) were used in this study. Toxocariasis was suspected based on clinical manifestations and confirmed by anti-toxocara IgG and Western blot analysis. Systemic albendazole (adults: 800 mg b.i.d.; children: 400 mg b.i.d.) was given in conjunction with steroids. Visual acuity before and after therapy, inflammatory response, side effects and toxicity were evaluated. Treatment resulted in an improved visual acuity in all patients. Mean initial Snellen visual acuity was 20/40, and mean final acuity was 20/20. There were no recurrences of uveitis throughout the observation period (average: 13.8 months; range: 3 days to 24 months). These findings suggest that albendazole, in combination with systemic steroids, is a useful regimen to treat ocular larva migrans syndrome.

16S rDNA-based identification of bacteria from conjunctival swabs by PCR and DGGE fingerprinting.

PURPOSE: Establishment of a new molecular biology technique for the identification of multiple bacteria from the ocular environment, which can be applied supplementarily to cultivation in cases of severe bacterial infections. METHODS: From 60 human conjunctivae (29 with purulent and 31 with nonpurulent conjunctivitis), swabs were taken and DNA was extracted. Fragments of 200 bp, spanning the V3 region of the eubacterial 16S rDNA, were amplified by polymerase chain reaction (PCR) and separated by denaturing gradient gel electrophoresis (DGGE). For phylogenetic identification, DGGE bands were excised and directly sequenced, or 16S rDNA clone libraries were constructed and clones were screened by DGGE. Sequences were compared with sequences of known bacteria listed in the EMBL database. Furthermore, the results were compared with results obtained from conventional cultivation. RESULTS: 16S rDNA could be amplified from 25 of 29 investigated swabs taken from purulent conjunctivitis eyes and from 2 of 31 investigated swabs taken from nonpurulent conjunctivitis eyes. Sixteen samples showed monomicrobial and 11 samples showed polymicrobial infections. The following genera (n is number of samples) were detected: Staphylococcus (n = 8), Corynebacterium (n = 7), Propionibacterium (n = 7), Streptococcus (n = 6), Bacillus (n = 2), Acinetobacter (n = 3), Pseudomonas (n = 3), Proteus (n = 1), and Brevundimonas (n = 1). Four sequences could not be identified to the genus level. They had highest sequence similarities both to sequences of Pantoea and Enterobacter (n = 1), Kingella and Neisseria (n = 1), Serratia and Aranicola (n = 1), and Leuconostoc and Weissella (n = 2), respectively. Culture was only positive for coagulase-negative staphylococci (n = 9), Corynebacteria (n = 3), Staphylococcus aureus (n = 1), Streptococcus sp. (n = 1), Proteus sp. (n = 1), Klebsiella oxytoca (n = 1), and Pseudomonas aeruginosa (n = 1). In total, 45% of the 60 analyzed conjunctival swabs were PCR positive, whereas only 22% were culture positive. No sample positive by culture gave negative results by PCR. CONCLUSIONS: 16S rDNA sequence analyses and DGGE fingerprinting are appropriate methods for the detection and identification of monomicrobial as well as polymicrobial ocular infections of bacteria that might not be detected by conventional cultivation.

Corneal lathing using the excimer laser and a computer-controlled positioning system.

PURPOSE: To present the excimer laser corneal shaping system (ELCS-S), an add-on device to the Keratom, a commercially available 193-nm excimer laser built by Schwind. METHODS: The system is designed for the preparation of donor corneas under sterile conditions using the ultraviolet laser to offer greatest possible flexibility. Lenticules for planolamellar grafting and refractive epikeratoplasty, as well as donor buttons for penetrating keratoplasty can be computer-designed by the surgeon or technician and lathed with the system. RESULTS: Using the excimer laser corneal shaping system (ELCS-S) on human donor corneas, the central surface of the epikeratoplasty lenticule exhibited only narrow, flat concentric notches corresponding to the single lathing steps. Transmission electron microscopy revealed a damage zone of less than 0.3 microm in close approximation to the treated surface. The final thickness revealed a difference of less than +/-53 microm from the intended, initially programmed value. Ultrastructural studies showed the perpendicular stromal surface of the penetrating keratoplasty buttons to be smooth with minimal protrusion of Descemet's membrane. Endothelial injury was observed in a zone averaging between 40 and 100 microm adjacent to the cutting edge only. CONCLUSION: The excimer laser corneal shaping system (ELCS-S) allows a computer-controlled, surgeon-designed, sterile preparation of lamellar and penetrating corneal grafts with the use of the excimer laser. This could offer significant advantages in comparison to presently available systems for lamellar dissection and trephination.

[Ocular toxocariasis in Austria]. / Okuläre Toxokarose in Osterreich.

HISTORY AND CLINICAL FINDINGS: Two women (aged 21 and 44 years) were referred because of a suspect retinal lesion. An ophthalmological examination in both revealed prominent retinal granulomatous foci, probably ocular toxocariasis. Both women were otherwise well; both reported close contact with dogs. INVESTIGATIONS: Among a full array of laboratory tests the only major pathologic findings were high antibody titres against Toxocara canis (patient 1: 70 antibody units [AU]; patient 2: > 100 AU), specific antibodies in the ELISA and Western blot tests confirming the diagnosis of T. canis infection. DIAGNOSIS, TREATMENT AND COURSE: Both patients were treated with prednisolone (initially 75 mg/d, gradually decreasing over 4 months) and albendazole (2 x 800 mg/d for 6 days), with complete healing of the chorioretinal foci. CONCLUSION: General physicians as well as ophthalmologists should more often include Toxocara canis infection in the differential diagnosis, because the larvae, in their migration through the body, can infest various organs where they can cause inflammatory or allergic reactions.

Impact of growth factors on morphometric corneal endothelial cell parameters and cell density in culture-preserved human corneas.

PURPOSE: Donor corneas can be preserved for < or = 4 weeks in organ culture (31 degrees C) by using modified minimal essential medium (MEM). About one fifth of them have to be discarded, however, as disintegration of the endothelial cell monolayer-enhanced polymegethism, cell loss-occurs. The objective of this study was to investigate whether addition of insulin, dextran, and epidermal growth factor (EGF) makes corneal endothelial cells more viable, stable, and homogeneous. METHODS: Sixteen paired human donor corneas were cocultured in media supplemented with EGF and insulin-like growth factor (IGF) or in conventional modified MEM for 4 weeks. Endothelial parameters were evaluated at the outset and at days 7, 14, 21, and 28 of culture by using an automated digital image-analysis system. RESULTS: No significant differences were observed in the first 2 weeks of culture. Beginning with day 14, however, stabilization of endothelial cell patterns was evident for corneas cultured in supplemented culture media. CONCLUSION: Our data indicate that the addition of growth factors to culture media might increase the percentage of corneas available for transplantation and would also allow a significantly longer period of preservation.

Ultrasound biomicroscopy of tangential keratotomy incision depth after penetrating keratoplasty.

PURPOSE: To assess the accuracy and reproducibility of using ultrasound biomicroscopy to measure corneal refractive incisions in vivo. SETTINGS: Department of Ophthalmology, University of Vienna, Austria. METHODS: Ultrasound biomicroscopy was performed in five eyes of five patients who had previous tangential keratotomy for high postkeratoplasty astigmatism. Depth of the incision scar was documented, and the measurements were compared with those obtained preoperatively by ultrasound pachymetry readings of the corneal thickness and with the settings of the diamond knife blade. RESULTS: The measured depths reached 84.7% +/- 12.9 (SD) of corneal thickness compared with the intended 89.1 +/- 6.7% depth of incision. The relation between knife setting and achieved depth was 95.3 +/- 15.9%. CONCLUSION: Ultrasound biomicroscopy provided high-quality images of the incision scars, accurately measuring actual incision depth in vivo. It may become a clinically useful tool for the refractive surgeon as it contributes to the predictability and accuracy of keratorefractive procedures.

Automated digital image analysis of organ culture preserved donor corneas.

The present study reports the application of a modified commercially available automated digital image analysis system (DIA) for the evaluation of organ culture preserved donor corneas. The central corneal endothelium was viewed and photographed under an inverted phase-contrast microscope. The images were then analyzed with the help of DIA. The results of DIA were compared to the findings obtained with a conventional 'fixed-frame analysis' for the same corneas. 100 human donor corneas have been evaluated. DIA, with interactive picture enhancement, was found to be practicable, and to yield reproducible results. The mean number of cells analyzed per photograph was 250 (range 95-395); this, on the average, was four times higher than with conventional fixed-frame analysis (mean 54, range 37-70). The correlation of the cell densities obtained with both methods was highly significant (p < 0.0001). Since additional information, like variation in cell size and shape (circularity form factor), was automatically computed by the program, more data on the homogeneity of the donor endothelial cell pattern were available. Furthermore, this computerized technique does not require an experienced investigator and thereby helps to eliminate bias.