Irene Ruhswurm

Astigmatism correction with a foldable toric intraocular lens in cataract patients.

PURPOSE To determine the efficacy and rotational stability of a toric posterior chamber silicone intraocular lens (IOL) to correct preoperative astigmatism in cataract patients. SETTING Department of Ophthalmology, University Hospital of Vienna, Vienna Austria. METHODS Between 1993 and 1998, foldable toric single-piece plate-haptic silicone IOLs were implanted in 37 eyes (30 patients). The cylindrical IOL power was 2.00 diopters (D) (n = 29), 3.50 D (n = 7), or 4.00 D (n = 1). Phacoemulsification was performed through a scleral or a corneal sutureless self-sealing incision. Outcomes of Snellen visual acuity (without, with spherical, and with best correction), refractive and keratometric astigmatism, and IOL rotation after early postoperative (mean 15.9 days +/- 10.1 [SD]) and long-term (mean 20.3 +/- 16.6 months) follow-ups were evaluated. RESULTS At last follow-up, 31 eyes (83.8%) had a spherically corrected and 34 (91.9%) a best corrected visual acuity of 0.5 (20/40) or better. Mean preoperative refractive and keratometric astigmatism was 2.68 and 2.70 D, respectively. At the last postoperative follow-up, mean refractive astigmatism was reduced to 0.84 D; keratometric astigmatism was 2.30 D. In 7 eyes (18.9%), the IOL axis was rotated a maximum of 25 degrees. In all 37 eyes, the axis of the toric IOL remained within 30 degrees of rotation. CONCLUSIONS Early postoperative and long-term follow-ups showed effective and stable correction of astigmatism after implantation of a foldable toric posterior chamber silicone IOL.

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma

BACKGROUND AND PURPOSE To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Three-year clinical outcome after penetrating keratoplasty for keratoconus with the guided trephine system

PURPOSE To determine the long-term clinical outcome after keratoplasty with the guided trephine system in keratoconus eyes. METHODS In a prospective study, all consecutive cases of penetrating keratoplasty had trephination performed with the guided trephine system, with which both donor and recipient cornea are trephined from the epithelial side with a same-sized blade. For wound closure, a double running antitorque suture technique with 10-0 nylon was used. Uncorrected and best-corrected Snellen visual acuity, subjective refraction, and astigmatism by keratometry were evaluated after final suture removal, 2 and 3 years postoperatively. RESULTS In the 31 patients (31 eyes) enrolled, mean best-corrected visual acuity improved from 0.72 +/- 0.16 (20/30) after final suture removal to 0.88 +/- 0.15 (20/25) 3 years postoperatively (P < .001). The mean spherical equivalent increased from -0.86 +/- 2.10 diopters after final suture removal to -2.35 +/- 2.65 diopters 3 years postoperatively (P < .001). Mean keratometric astigmatism decreased from 4.68 +/- 1.76 diopters after final suture removal to 3.57 +/- 1.37 diopters 3 years postoperatively (P = .001). Furthermore, an increase in mean keratometric levels with time (P = .01) was observed and associated with myopic shift (r(s) = -.46, P = .008). CONCLUSION With the guided trephine system, we attained favorable visual results, with prolonged improvement of visual acuity during the entire follow-up period. Our data show low and decreasing degrees of corneal astigmatism over time. During the follow-up period, a myopic shift was found after final suture removal. Nevertheless, this technique of performing same-sized grafts reduces postoperative residual myopia.

Ophthalmic and Genetic Screening in Pedigrees With Familial Adenomatous Polyposis

PURPOSE To study the possible association between ophthalmic findings, genetic status, and clinical course of the disease in Austrian pedigrees with familial adenomatous polyposis (FAP). METHODS Thirty-nine members of 16 consecutive FAP families with 20 affected patients and 19 relatives with a 50% a priori risk to develop the disease were examined ophthalmologically. The intestinal status of all persons was established by colonoscopy. Direct or indirect molecular genetic analysis, or both, was possible in eight of the 16 FAP families. RESULTS Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was discovered in 15 (75%) of the 20 persons affected by familial adenomatous polyposis. Five (25%) of the patients with an established FAP were CHRPE-negative. Four of the 19 at-risk individuals were CHRPE-positive. According to DNA analysis, five of the 19 at-risk relatives had a high risk to develop a manifest disease. The ophthalmoscopic tests were in complete agreement with the molecular risk estimation. Furthermore, the combined results of endoscopy and ophthalmoscopy suggested a relationship between a positive CHRPE status and the severity of FAP. CONCLUSIONS Ophthalmic examinations facilitate predictive diagnosis in FAP patients and first-degree relatives, permitting a noninvasive, highly reliable risk assessment. When present, CHRPE lesions are a reliable clinical marker for FAP in CHRPE-positive families. In CHRPE negative families, negative ophthalmic examinations are of no predictive value. The CHRPE status can add information about the location of the genetic mutation. The combination of an ophthalmic examination with DNA analysis and endoscopy improves the risk assessment of FAP carriers.

Tumour Regression of Uveal Melanoma after Ruthenium-106 Brachytherapy or Stereotactic Radiotherapy with Gamma Knife or Linear Accelerator

Purpose: This study assesses differences in relative tumour regression and internal acoustic reflectivity after 3 methods of radiotherapy for uveal melanoma: (1) brachytherapy with ruthenium-106 radioactive plaques (RU), (2) fractionated high-dose gamma knife stereotactic irradiation in 2–3 fractions (GK) or (3) fractionated linear-accelerator-based stereotactic teletherapy in 5 fractions (Linac). Methods: Ultrasound measurements of tumour thickness and internal reflectivity were performed with standardised A scan pre-operatively and 3, 6, 9, 12, 18, 24 and 36 months postoperatively. Of 211 patients included in the study, 111 had a complete 3-year follow-up (RU: 41, GK: 37, Linac: 33). Differences in tumour thickness and internal reflectivity were assessed with analysis of variance, and post hoc multiple comparisons were calculated with Tukey’s honestly significant difference test. Results: Local tumour control was excellent with all 3 methods (>93%). At 36 months, relative tumour height reduction was 69, 50 and 30% after RU, GK and Linac, respectively. In all 3 treatment groups, internal reflectivity increased from about 30% initially to 60–70% 3 years after treatment. Conclusion: Brachytherapy with ruthenium-106 plaques results in a faster tumour regression as compared to teletherapy with gamma knife or Linac. Internal reflectivity increases comparably in all 3 groups. Besides tumour growth arrest, increasing internal reflectivity is considered as an important factor indicating successful treatment.

FRACTIONATED STEREOTACTIC RADIOTHERAPY WITH LINEAR ACCELERATOR FOR UVEAL MELANOMA - PRELIMINARY VIENNA RESULTS

PurposeTo study local tumor control and radiogenic side-effects after fractionated stereotactic radiotherapy for uveal melanoma.Patients and MethodsBetween June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with a stereotactic 6 MeV LINAC (Saturne 43®, General Electric, France) in conjunction with a stereotactic frame system (Brain LAB®, Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0±2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment.ResultsAfter a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed.ConclusionOptical fixation of the eye allows high precision stereotactic radiotherapy with small safety margins. Fractionated stereotactic radiotherapy and 70 Gy total dose delivered in 5 fractions seems to be appropriate for local tumor control in uveal melanoma. Further long-term studies with extended number of patients will be necessary to conclude on the use of linac-based fractionated stereotactic radiotherapy for uveal melanoma.

Effect of tenascin and fibronectin on the migration of human corneal fibroblasts

Purpose: To investigate the effect of fibronectin and tenascin on the migration of corneal fibroblasts. Setting: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. Methods: Using human corneal fibroblasts, a monolayer migration assay was performed to measure corneal fibroblast movement. The migration on collagen I, fibronectin, and tenascin with and without transforming growth factor (TGF)‐&agr;/fibroblast growth factor (FGF)‐2 stimulation and the effect of soluble tenascin and fibronectin on corneal fibroblast migration on collagen‐I‐coated wells were investigated. Results: The cytokines TGF‐&agr; and FGF‐2 stimulated migrational activity of corneal stromal cells in a dose‐dependent manner, reaching the maximum effect at 100 ng/mL and 10 ng/mL, respectively. The migration of corneal fibroblasts on fibronectin was significantly higher (P < .05) than the migration on collagen I. Transforming growth factor‐&agr; and FGF‐2 increased radial cell displacement independent of the provided matrix composition. Tenascin had a negative effect on corneal fibroblast adhesion/migration in this in vitro model. Conclusion: Fibronectin and tenascin influenced corneal fibroblast migration and adhesion, respectively, and may play a role in stromal cell movement during wound healing. The cytokines TGF‐&agr; and FGF‐2 had an additive effect on corneal fibroblast migration on a fibronectin matrix.

Ocular arterial blood flow of choroidal melanoma eyes before and after stereotactic radiotherapy using Leksell gamma knife: 2 year follow up

AIMS To evaluate the effect of high dose stereotactic radiotherapy on the ocular blood flow of patients with uveal melanoma. METHODS Colour Doppler imaging (CDI) was used to measure blood flow velocity and vascular resistance in the ophthalmic, short posterior, and central retinal arteries of nine patients suffering from uveal melanoma. The measurements were taken before, 6 months, 1 year, and 2 years after stereotactic radiotherapy. Irradiation was performed with the Leksell gamma knife with the 59 (41–66.5) Gy total marginal dose divided in two equal fractions. CDI results were compared with age and sex matched healthy control eyes. RESULTS At each time of measurement, blood flow velocity in the central retinal artery of the affected eyes was significantly reduced whereas vascular resistance was only increased at the 2 year follow up. Blood flow velocity and vascular resistance in the short posterior arteries of melanoma eyes were also only significantly altered at the 2 year follow up. Blood flow velocity and vascular resistance in the ophthalmic artery of melanoma eyes were not changed at all follow ups. CONCLUSIONS In the melanoma eyes, blood flow velocity in the central retinal artery is reduced. High dose stereotactic radiotherapy with the Leksell gamma knife and a 59 (41–66.5) Gy total marginal dose in two fractions leads to a significant reduction of blood flow and a significant increase in resistance variables in the small ocular arteries within 2 years.

Evaluation of cytomegalovirus retinitis management. Outcome of four years of cytomegalovirus therapy.

Cytomegalovirus (CMV) is the most common pathogen of opportunistic viral infections in patients with the acquired immunodeficiency syndrome. In this study, we assessed the therapeutic outcome of our treatment regimen of CMV retinitis by analysing retrospectively 33 consecutive patients. The clinical utility of CMV cultures from blood, urine and throat specimens obtained at the time of diagnosis was additionally evaluated. Treatment started with ganciclovir (GCV) therapy. In case of relapsing retinitis, re-induction therapy was initiated, and if unsuccessful, the patient was switched to foscarnet. Patients developing resistant retinitis despite foscarnet therapy were offered a GCV-foscarnet combination therapy. Under primary GCV therapy, the median first stable interval of the whole group was 202 days (mean 238 days). Twenty-five out of 33 CMV retinitis patients (76%) responded to initial GCV therapy. Eleven of these patients showed relapsing retinitis that could be stabilised in 3 patients solely with combination therapy. Eight patients did not respond to primary GCV therapy. Three of them improved with foscarnet, but 3 patients did not respond to either treatment. In 18 (56%) out of 32 patients, CMV cultures yielded positive results. Considering our series, we may conclude that in the majority of patients primary or secondary viral resistance can be overcome by dose increase, switching to the alternative drug or a combination therapy.

Stereotaktische Bestrahlung uvealer Melanome: Erste Wiener Ergebnisse

ZusammenfassungHintergrundDie stereotaktische Bestrahlung uvealer Melanome stellt einen neuen Therapieansatz dar. Vorliegende Studie untersucht die lokale Tumorkontrolle und Nebenwirkungen nach stereotaktischer Teletherapie uvealer Melanome mit einer Dosis zwischen 41 und 71 Gy.Technik und PatientenSeit Oktober 1993 wurden 82 Patienten stereotaktisch bestrahlt. In keinem Fall lag eine Vorbehandlung oder Metastasen vor. Im Zeitraum Oktober 1993 bis April 1997 wurden 62 Patienten mit der Gamma Unit (Gamma Knife®, Elekta, Schweden) und einer Dosis zwischen 41 und 71 Gy bestrahlt. Die mittlere Randdosis betrug 55 ± 9 Gy. Die mittlere Tumordicke lag vor Behandlung bei 7,8 ± 2,7 mm. 41 Patienten (66%) wurden mit 2 gleich großen Fraktionen (2 × 35 bis 2 × 27 Gy) behandelt. 7 Patienten (11%) wurden radiochirurgisch mit 45 Gy bestrahlt. Von August 1996 bis April 1997 wurden 14 Patienten (23%) mit einer Gesamtdosis von 45 Gy, aufgeteilt in 3 Fraktionen von je 15 Gy behandelt. In Zeitraum Juni 1997 bis Februar 1998 wurden 20 Patienten mit einem stereotaktischen Linearbeschleuniger (Saturne 43®, General Electric, Frankreich) in Verbindung mit einem stereotaktischen Maskensystem (BrainLAB®, Deutschland) und 70 Gy in 5 bis 7 Fraktionen bestrahlt. Die mittlere Tumordicke vor Behandlung betrug 6,0 ± 2,2 mm.ErgebnisseFür die 62 Gamma Knife-Patienten beträgt der mittlere Nachbeobachtungszeitraum 28 ± 11 Monate. Bei 61 Augen (98%) konnte ein weiteres Tumorwachstum verhindert werden. Lediglich einmal (2%) trat ein Randrezidiv auf. 54 Augen (87%) konnten erhalten werden. 23 Patienten entwickelten eine Katarakt, 18 eine Uveitis, 12 ein Sekundärglaukom, 14 eine Retinopathie, 16 eine Optikusneuropathie und 8 eine Metastasenerkrankung. Bislang sind sechs Patienten an Metastasen verstorben. Eine Multivarianzanalyse der ersten 48 Patienten zeigte, daß das ursprüngliche Tumorvolumen den wichtigsten prognostischen Faktor sowohl für die Entwicklung einer Sekundärkatarakt als auch eines Sekundärglaukoms darstellt. Dagegen korrelierten Uveitis, Retinopathie und Optikusneuropathie mit dem Volumen, das mit mehr als 25 Gy/Fraktion bestrahlt worden war. Bei den Patienten, die seit Juni 1997 mit dem LINAC und mit 5 bis 7 Fraktionen behandelt worden waren, wurden bislang keine intraokulären bzw. nur geringe subakute radiogene Nebenwirkungen an Lidern und der Bindehaut beobachtet. 11 von 12 Patienten mit einer Beobachtungszeit von mehr als 3 Monaten zeigten eine lokale Tumorkontrolle.ZusammenfassungDie stereotaktische Strahlentherapie mit 41 bis 71 Gy kann erfolgreich zur lokalen Tumorkontrolle uvealer Melanome eingesetzt werden. Die radiogenen Spätschäden im Vorderabschnitt des Auges sind in erster Linie mit dem ursprünglichen Tumorvolumen verbunden. Die Spätschäden im Hinterabschnitt des Auges (Optikusneuropathie, Uveitis und Retinopathie) hingegen korrelieren mit der Dosis/Fraktion.SummaryPurposeTo study local tumour control and radiogenic side-effects after stereotactic photon radiotherapy for uveal melanoma, using a tumorcidal dose between 41 and 71 Gy.Technique and PatientsSince October 1993, a total of 82 patients with uveal melanoma without prior treatment or metastasis at baseline have been treated with stereotactical photon beam external radiotherapy, either with the Gamma Unit (Gamma Knife®, Elekta, Sweden) or a stereotactic LINAC. Between October 1993 and April 1997, 62 patients with uveal melanoma were irradiated with the Gamma using dose between 41 and 71 Gy. Mean marginal dose was 55 ± 9 Gy. Mean tumour prominence before treatment was 7.8 ± 2.7 mm. In 41 patients (66%), the total dose was divided into two equal fractions, ranging from 2 × 35 to 2 × 27 Gy. 7 patients (11%) were irradiated with one fraction of 45 Gy. Between August 1996 and April 1997, 14 patients (23%) have been treated 3 fractions of 15 Gy each (45 Gy total marginal dose).Between June 1997 and February 1998, 20 patients have been treated with a stereotactic LINAC (Saturne 43®, General Electric, France) in conjunction with a stereotactic frame system (BrainLAB®, Germany). A total marginal dose of 70 Gy was divided into 5 to 7 fractions. Median tumour prominence before treatment was 6.0 ± 2.2 mm.ResultsFor the 62 patients treated with the Gamma Unit, average follow-up time is 28 ±11 months. Further tumour growth was stopped in all but one eye (98%). In one case (2%) a marginal reoccurrence was observed. 54 eyes (87%) could be preserved. 23 patients developed cataract, 18 uveitis, 12 secondary glaucoma, 14 retinopathy, 16 optic neuropathy and 8 metastatic disease — six of them have died. For the first 48 patients a step-by-step multivariate analysis revealed initial tumour volume as the most important factor for the development of secondary cataract and glaucoma. The tissue volume irradiated with 25 Gy or more/fraction was most predictively for the occurrence of uveitis, retinopathy and optic neuropathy. In the patients treated with the stereotactic LINAC, only mild subacute radiogenic side-effects at the lids and conjunctiva but no intraocular side-effects were observed. In 11 of 12 cases with a follow-up period exceeding three months, local tumour control was noticed echographically.ConclusionsStereotactic photon beam radiotherapy with 41 to 71 Gy is effective for the local tumour control in patients with uveal melanoma. Complications in the anterior segment of the eye are mainly related to the initial tumour volume. Posterior segment complications (optic neuropathy, uveitis and retinopathy) are significantly correlated the dose/fraction.