Harald Schilling

Long term results after low dose ocular irradiation for choroidal haemangiomas

AIM/BACKGROUND The most common choice of treatment for choroidal haemangiomas (CH) in the past has been the employment of scatter photocoagulation of the surface. This management often requires repetitive treatment or additional invasive management due to massive exudative detachment of the retina. The aim of this retrospective study was to investigate the outcome of the alternative application of low dose external beam irradiation with high energetic photons on these tumours. METHODS A total absorbed dose of 20 Gy was applied to a total of 51 symptomatic eyes: 36 with a circumscribed CH of the posterior pole and 15 with diffuse CH as part of the Sturge–Weber syndrome. The indication for treatment was an exudative retinal detachment including or threatening the fovea. The mean follow up times in each group were 4.5 and 5.3 years, respectively. Out of a group of 33 patients from whom reliable data could be derived, 17 had symptoms lasting longer than 6 months. RESULTS In 23 cases (63.8%) with circumscribed CH complete resolution of the subretinal fluid was achieved; the remaining 13 cases (36.2%) showed residual serous detachment distant to the fovea. The visual acuity improved by two or more lines in 14 cases (38.9%), remained stable in 14 cases (38.9%), and decreased in eight cases (22.2%). The functional success was dependent on the lag duration between onset of first subjective symptoms and treatment. The morphological results with diffuse CH were similar to those of the group of circumscribed CH. The visual acuity (VA) at last examination was improved in seven cases (46.6%); in the remaining eight cases, VA was unchanged or had deteriorated. The poor functional outcome in the latter was mainly attributable to secondary glaucoma. CONCLUSION External beam irradiation is a useful and a low invasive therapeutic option for CH. A successful functional outcome is dependent on the time delay between first onset of symptoms and the beginning of therapy, the formation of subretinal fibrosis, and also on secondary glaucoma in the case of Sturge–Weber syndrome.

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma

Aim: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. Methods: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m2 body surface area and a light dose of 100 J/cm2 at 692 nm. Results: The mean follow up time was 10.6 months (2–24 months). The mean number of treatment sessions was 2.15 (range 1–5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. Conclusion: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

Histopathologic findings in eyes treated with a ruthenium plaque for uveal melanoma

Fifty-six globes that had to be enucleated following ruthenium plaque therapy were examined histopathologically. These eyes account for 10% of all uveal melanomas treated at the University Eye Clinic Essen up until 1985. All but one revealed at least some supposedly viable tumor cells. The most prominent findings within the tumors were tumor cell necrosis, vacuolization and balloon cell degeneration, vascular obstruction and fibrosis of the tumor stroma with accumulation of pigmented macrophages. Tumor necrosis was complete or nearly complete in five cases. Tumor regression correlated with cell type and pigmentary characteristics of the tumor, with epithelioid and heavily pigmented tumor cells being more radiosensitive. Tumor regression was inhomogeneous, possibly due to polyclonality, with tumor cells of varying radiosensitivitiy, or due to patchy areas of vascular obliteration. Among other ocular structures, extensive subretinal gliosis, chorioretinal atrophy and scarring of the sclera within the field of radiation were observed. Scleral necrosis was present in only five cases and was limited to areas in which the tumor had infiltrated the deep scleral layers. The findings described were considered to reflect radiation injury rather than spontaneous tumor regression when compared to 70 control eyes that had been enucleated without prior treatment for uveal melanoma.

Expression of the Cell Adhesion Molecules ICAM-1, VCAM-1 and NCAM in Uveal Melanoma: A Clinicopathological Study

To investigate the relationship between the expression of the cell adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) in uveal melanoma and the metastatic spread in the first 5 years after diagnosis, we performed a hospital-based case-control study with human tissue from 90 patients who underwent enucleation for primary uveal melanoma (iris melanoma excluded). Thirty-five patients developed metastasis within the first 5 years, and 55 patients lived metastasis-free for at least 5 years after enucleation. The paraffin-embedded and formalin-fixed globes were studied by immunohistochemistry with monoclonal antibodies for ICAM-1, VCAM-1 and NCAM. A strong ICAM-1 positivity (more than 75% of the tumor cells stained positive) was detected in 73 tumors (81%). The expression of 75% or less ICAM-1 positive cells in tumors was strongly associated with the development of metastases (odds ratio: 7.5, p = 0.001). Multiple logistic regression models showed that ICAM-1 is an independent risk factor for metastasis even after control for important prognostic markers like extraocular growth, ciliary body involvement, scleral infiltration and cell type. VCAM-1 was expressed in 24 out of 88 tumors (27.3%) and NCAM only in 14 out of 87 tumors (16%). Only spindle cells stained positive with anti-NCAM. NCAM and VCAM-1 expression was not related to metastasis. Our results show that the loss of ICAM-1 expression is associated with an increased risk of metastasis within the first 5 years after diagnosis.

Ruthenium-106 plaque brachytherapy for symptomatic vasoproliferative tumours of the retina.

Aim: To investigate the safety and efficacy of β ray brachytherapy in treatment of vasoproliferative tumours of the retina (VTR). Methods: 35 consecutive patients with symptomatic VTR were treated with a ruthenium-106 (106Ru) plaque. Three tumours had been treated previously (two with cryotherapy; one with transpupillary thermotherapy). 32 VTR (91.4%) were located in the lower half of the retina and all of them were found between the mid-periphery and the ora serrata. The mean tumour thickness was 2.8 mm. An exudative retinal detachment was present in 25 eyes (71.4%) and in 15 cases (42.9%) hard exudates were found in the macula. The major symptom was loss of vision (77.1%). Results: Brachytherapy was well tolerated by every patient. The mean applied dose was 416 Gy at the sclera and 108 Gy at the tumour apex. In all but four eyes (88.6%), it was possible to control the VTR activity. The median follow up time was 24 months. Three of the above mentioned four eyes with treatment failure had had secondary glaucoma before therapy. There was no case of radiation induced neuropathy or retinopathy. Cataract surgery was necessary for five patients. The development of epiretinal gliosis was the most common event during follow up (n = 10, 28.6%). The mean visual acuity decreased slightly (0.33 before and 0.29 after brachytherapy). Multivariate analysis showed that the presence of macular pathology before treatment was associated with a 6.1-fold risk of vision of 0.25 or better (p = 0.03). Conclusions: β ray brachytherapy with 1106Ru plaques was able to control the activity of VTR and retain vision. Cases with secondary glaucoma before treatment had a very poor prognosis.

Higher vessel densities in retinoblastoma with local invasive growth and metastasis.

In this study, the importance of angiogenesis (the growth of new blood vessels from existing ones) for the growth of retinoblastoma was investigated by a retrospective immunohistochemical analysis. An individual vessel index for each tumor was determined using the endothelial-specific antibody CD 31 for vessel staining. The obtained data were correlated with clinical features, pathohistological characteristics, and the presence of metastasis. In 107 retinoblastomas collected between 1980 and 1990, we found no difference in the vessel densities between uni- and bilateral retinoblastomas (P = 0.41). However, tumors that had invaded the chorioid and/or the optic nerve statistically showed higher vessel densities than tumors without local invasive growth (P = 0.05 and P = 0.024). A tendency of higher vessel densities in retinoblastomas presenting with metastasis at the time of diagnosis was observed (P = 0.11). Based on this observation, we proceeded to examine all retinoblastomas presenting with metastasis at the time of diagnosis. These included patients that were treated between 1968 and 1993. The 18 investigated retinoblastomas had significantly higher vessel densities than all other retinoblastomas presenting without metastasis (P = 0.025). Our data indicate that in retinoblastoma, blood vessels are essential for local and systemic invasive growth. Therefore, an anti-angiogenic therapy could be considered in the multimodal therapy concept for retinoblastomas with invasive growth, both locally and systemically.

Endoresektion maligner Melanome der Uvea nach präoperativer stereotaktischer Einzeldosis-Konvergenzbestrahlung mit dem Leksell-Gamma-knife

ZusammenfassungDurch konventionelle strahlentherapeutische Verfahren ist bei großvolumigen und hochprominenten Melanomen der Uvea der Erhalt des Bulbus oder gar einer Restfunktion des betreffenden Auges nur selten möglich. Komplikationen aufgrund des massiv anfallenden nekrotischen Gewebes zwingen häufig zu einer späteren Enukleation des dann erblindeten Auges. Eine tumorzerstörende Einzeldosis-Konvergenzbestrahlung (Radiochirurgie) solcher Tumoren vor einer zeitnah danach durchzuführenden Endoresektion kann eine gangbare therapeutische Alternative in derartigen Fällen darstellen.AbstractIn cases of large volume and highly prominent melanomas of the uvea, it is rare for conventional methods of radiation therapy to enable salvage of the globe or even residual functionality of the affected eye. Complications due to the massive amount of accumulated necrotic tissue often necessitate subsequent enucleation of the blinded eye. Tumor-destroying, single-dose convergence irradiation (radiosurgery) of such tumors applied shortly before endoresection can represent a possible therapeutic alternative in these types of cases.

Combined phacoemulsification and pars plana vitrectomy: Clear corneal versus scleral incisions Prospective randomized multicenter study

Purpose: To compare the complications and outcomes of implantation of a foldable intraocular lens (IOL) through a clear corneal incision and implantation of a poly(methyl methacrylate) (PMMA) IOL through a scleral incision in combined phacoemulsification and pars plana vitrectomy. Setting: Departments of Ophthalmology, St. Franziskus Hospital, Muenster, Eye Hospital, Muelheim, and University of Essen, Essen, Germany. Methods: This prospective randomized study included 62 eyes having implantation of a PMMA IOL (811B, Pharmacia) through a scleral incision and 61 eyes having implantation of a polyacrylic (AcrySof®, Alcon) IOL through a clear corneal incision. The preoperative visual acuity, underlying retinal disease, and vitreoretinal surgical maneuvers did not differ between groups. The surgical methods and intraoperative complications were noted. Examinations 2 days and 3 months after surgery included visual acuity, refractive error, keratometry, slitlamp evaluation, tonometry, and ophthalmoscopy. Results: Intraoperatively, both incisions were stable and no serious complications occurred. Two days after surgery, the incidence and quantity of cells and fibrin in the anterior chamber were lower in the clear corneal incision group than in the scleral incision group (P<.05). Corneal endothelial dysfunction was more common in the clear corneal group than in the scleral group (P<.05). Three months after surgery, the astigmatic changes did not differ significantly between groups and the incidence of posterior capsule opacification (PCO) was lower in the clear corneal group (P<.05). Postoperative visual acuity improved significantly in 63% of eyes and 61% of eyes in the scleral group and clear corneal group, respectively. Visual acuity was limited by macular pathology. Conclusions: Both clear corneal and scleral incisions were safe in combined phacoemulsification and vitrectomy. Eyes with smaller clear corneal incisions and foldable IOLs had less postoperative inflammation and PCO.

Long-term effect of acetazolamide treatment of patients with uveitic chronic cystoid macular edema is limited by persisting inflammation.

Purpose: To assess the long-term effect of acetazolamide treatment on patients with cystoid macular edema (CME) in the course of intermediate or posterior chronic uveitis and to define those patients who may particularly benefit from the drug. Methods: Fifty-two eyes (45 patients) with chronic uveitic CME were treated with acetazolamide at an initial dosage of 500 mg/d. The effect of treatment was assessed by fluorescein angiography, ophthalmoscopy, visual acuity, and Amsler testing. Therapy was withdrawn when CME did not improve at 3 weeks. In cases with CME improvement, the dosage was gradually tapered. Results: The mean follow-up was 3.1 years (minimum, 1.5 years). Two subgroups were identified: group 1, quiescence of uveitis with acetazolamide as the single therapeutic agent (33 eyes); and group 2, chronically active uveitis requiring additional systemic antiinflammatory drugs (19 eyes). In both groups, visual acuity improvement was statistically significant (group 1, P = 0.012; group 2, P = 0.025). In 12 patients with a stable visual acuity gain, the medication dose could be tapered off completely without any recurrent edema shown by fluorescein angiography after a minimum follow-up of 1 year. Sixteen patients required a maintenance dosage, ranging from 125 to 500 mg daily. No major adverse effects of the medication were observed. Conclusions: During long-term follow-up, low-dose acetazolamide can be a useful therapeutic option for chronic CME in uveitis. The effect was better in patients with quiescence of uveitis than in those with chronically active uveitis. Permanent therapy is not imperative in every case.

Photodynamic therapy using verteporfin for choroidal neovascularization associated with angioid streaks--long-term effects.

Aim: To investigate the safety and efficacy of photodynamic therapy with verteporfin (PDT) in patients with choroidal neovascularization associated with angioid streaks (CNVAS). Methods: A nonrandomized, prospective clinical investigation of 12 patients with CNVAS was performed. PDT was based on the criteria concerning the treatment of age-related macular degeneration. Results: The mean follow-up was 41.75 months (range 24–60). The mean number of (re)treatments was 3.3 (range 2–7). Visual acuity improved by at least 1 line in 42%, was stable within ±2 lines in 33%, decreased by at least 1 line in 58% and by >3 lines in 25% of the patients. The mean visual acuity was 0.30 (range 0.2–0.5) prior to and 0.17 (range 0.03–0.6) after the final PDT. The mean visual acuity of the contralateral eye was 0.1. 75% of contralateral eyes and 25% of the treated eyes had a final visual acuity of ≤0.1 (20/200). At the final follow-up, a significant enlargement of the lesion size was noted in 92% of the cases. Conclusion: Using the current (re)treatment criteria, PDT does not appear to limit the growth of CNVAS. Compared to the aggressive natural course and to the limited treatment options, PDT may at least in part help to stabilize macular function over a limited period of time.