Grading choroidal neovascular membrane regression after strontium plaque radiotherapy; masked subjective evaluation vs planimetry.

PURPOSE: To analyze angiographic changes in choroidal neovascular membranes (CNVM) after strontium-plaque (90Sr) irradiation for exudative age-related macular degeneration (AMD) using masked measurement of the CNVM areas and a masked subjective comparison of CNVM size and leakage. METHODS: We studied the baseline, 3, 6, and 12-month angiograms of 19 eyes treated with 90Sr-plaque irradiation for exudative AMD. The area of CNVM-related hyperfluorescence was measured quantitatively, and the angiograms were subjectively evaluated by a masked grader. RESULTS: In 7 of the 19 eyes the CNVM-related hyperfluorescence was too scattered to be analyzed by planimetry but masked subjective grading correlated with the clinical response to irradiation. In the remaining 12 eyes, the CNVM decreased in size in 67% of the eyes and showed leakage in 67%. Planimetry and subjective assessment of the size and leakage of the CNVMs similarly reflected the regression after irradiation. CONCLUSIONS: CNVM size and leakage frequently diminish after 90Sr-plaque irradiation. Quantitative measurement of the CNVM areas, or a grading system based on masked subjective assessment, give similar results for evaluating these changes. Masked subjective grading can be used even in cases where the CNVM is too scattered to be outlined for planimetry.

Retinal breaks before and after neodymium:YAG posterior capsulotomy.

PURPOSE: To determine the frequency of asymptomatic retinal breaks before and after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: Of 350 consecutive patients referred for their first laser Nd:YAG posterior capsulotomy, 235 eligible eyes were enrolled and 220 eyes completed the study. A vitreoretinal surgeon looked for retinal breaks using binocular indirect ophthalmoscopy with scleral indentation. The eyes were examined 1 week before and 1 hour and 1 month after the posterior capsulotomy. The number, type, and location of retinal breaks were recorded. RESULTS: The median age of eligible patients who did not participate in the study was higher than that of enrolled patients (79.6 versus 74.4 years; P =.0005). The mean axial length, median time from cataract surgery, and the course of cataract surgery were comparable in both groups. Before the posterior capsulotomy, an untreated retinal break was diagnosed in 4 of the 235 eyes (1.7%; 95% confidence interval [CI] 0 to 4) scheduled for surgery and an undiagnosed retinal detachment was present in 2 additional eyes (0.9%; 95% CI 0 to 3). An asymptomatic retinal break was also present in 4 fellow eyes (1.7%, 95% CI 0 to 4). No new breaks developed during Nd:YAG posterior capsulotomy using a median total energy of 51 mJ (range 10 to 901 mJ) and a median number of 22 applications (range 4 to 341 applications) and resulting in an opening with a median largest diameter of 3.4 mm (range 2.0 to 4.6 mm). In 1 treated eye (0.4%; 95% CI 0 to 2), a new retinal break had developed by 1 month postoperatively. CONCLUSIONS: The observed 2.1% frequency of asymptomatic retinal breaks that had escaped the attention of the referring ophthalmologist or had developed by 1 month after Nd:YAG posterior capsulotomy can be contrasted with the 0.5% to 2.0% frequency of retinal detachment reported in the literature. However, it is not known which proportion of such asymptomatic breaks, if any, will progress to detachment after Nd:YAG laser posterior capsulotomy.

Strontium plaque irradiation of subfoveal neovascular membranes in age-related macular degeneration.

PURPOSE: To determine the effect of focal strontium-90 plaque radiotherapy on subfoveal choroidal neovascularization in patients with age-related macular degeneration. METHODS: Twenty patients with age-related macular degeneration, presenting with a recent subfoveal neovascular membrane, were treated with local episcleral radiotherapy using a strontium-90 applicator. The applicator was applied to the sclera under the macular region and held there tightly for 54 min to obtain a dose of 15 Gy at a depth of 1.75 mm. The main parameters evaluated at follow-up after 3, 6 and 12 months were visual acuity and changes in fluorescein angiography. Twelve untreated patients with the same criteria were followed as controls. RESULTS: Early effects of radiation could be seen at 3 months, but became more obvious after follow-up for 6 and 12 months. At 6 months, regression of the choroidal neovascularization was detected in 14/19 patients (74%) as a decrease in the size of the lesion or as diminished leakage in late-phase fluorescein angiography. Likewise, in 14/19 patients (74%) at 12 months the neovascular membrane was partially or totally occluded. In all patients showing regression of the choroidal neovascular membrane, the neurosensory detachment had also dried. Visual acuity was unchanged (within 1 line) or improved in 11/20 (55%) and 9/20 (45%) treated patients after 6 and 12 months, respectively. In the controls, the choroidal neovascularization had increased in size in 9/12 patients (75%) at the last follow-up (mean 12.0 months). Visual acuity was unchanged in 3/12 patients (25%). CONCLUSION: Local low-energy beta irradiation with a strontium-90 applicator can induce regression of choroidal neovascularization. The effect of irradiation is seen as a decrease in the size of the choroidal neovascular membrane and disappearance of the neurosensory detachment and exudates.

Plasminogen activation in epiretinal membranes.

BACKGROUND: Formation of epiretinal membranes occurs in proliferative vitreoretinopathy, macular pucker and after penetrating trauma. Epiretinal membrane formation includes cell migration and proliferation, extracellular matrix formation and tissue contraction. Generally in scar tissue formation, the production of new extracellular matrix occurs concomitantly with its proteolytic degradation, resulting in continuous tissue remodelling. The plasminogen activator-mediated proteolytic cascade is an important mechanism for pericellular degradation of the extracellular matrix. Therefore we wanted to study the presence of the plasminogen activator-mediated proteolytic cascade in epiretinal membranes. METHODS: Specimens of 18 epiretinal and 3 subretinal membranes were obtained during vitreous surgery for retinal detachment with proliferative vitreoretinopathy or macular pucker. Plasminogen activators and plasmin were characterized in frozen sections of epiretinal membranes by in situ zymography and in membrane lysates by zymography. Indirect immunofluorescence staining was performed to localize urokinase in epiretinal membranes. RESULTS: Urokinase was present in 17/21 and tissue-type plasminogen activator in 12/21 of the membranes studied. Active plasmin was not detected in the frozen sections of epiretinal membranes. Immunofluorescence staining localized urokinase predominantly in the areas invaded by macrophages and cells of retinal pigment epithelial origin. CONCLUSION: Our results demonstrate the presence of proteolytic activity in periretinal scar tissue. Urokinase was more consistently present, but smaller amounts of tissue-type plasminogen activator were also found in the specimens. These results indicate that continuous tissue remodelling with simultaneous extracellular matrix production and breakdown regulates the growth of epiretinal membranes.

Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.

AIMS/BACKGROUND: To analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. METHODS: A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The median apical and scleral tumour dose was 100 Gy (range 15-200 Gy) and 1000 Gy (range 200-1200 Gy), respectively. The median follow up time was 2.8 and 2.0 years (range 1 month to 10 years) for anterior and posterior segment complications, respectively. RESULTS: The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. The risk of radiation cataract was highest with large tumour size (T1 + T2 v T3, p = 0.0027; height < or = 5 v > 5 mm, p = 0.029; largest basal diameter (LBD) < or = 15 v > 15 mm, p < 0.0001) and location of anterior tumour margin anterior v posterior to the equator (p = 0.0003); the risk of neovascular glaucoma with large size (T1 + T2 v T3, p = 0.039; LBD < or = 15 mm v 15 mm, p = 0.021); and the risk of maculopathy and optic neuropathy with proximity of the posterior tumour margin to the fovea and the optic disc (< or = 1.5 v > 1.5 mm; p = 0.030 and p = 0.0004, respectively). In Cox's multivariate analysis the strongest risk indicator for radiation cataract (RR 1.5, 95% CI 1.4-1.6) and vitreous haemorrhage (RR 1.6, 95% CI 1.4-1.8) was the height of the tumour; for neovascular glaucoma the TNM class (RR 6.2, 95% CI 2.7-13.8); for radiation maculopathy location of posterior tumour margin within 2 mm from the fovea (RR 3.4, 95% CI 2.0-6.0); and for radiation optic neuropathy location of tumour margin within 1 DD of the optic disc (RR 6.1, 95% CI 3.0-12.4). The 3 and 5 year probabilities of avoiding enucleation were 92% and 85%, respectively. Ten eyes were enucleated--six because of recurrent tumour growth, three because of treatment complications, and one because of mistakenly suspected extraocular growth. CONCLUSION: The results suggest that the frequency of radiation related complications after ruthenium brachytherapy of uveal melanoma is acceptable, in particular as regard irradiation of small and medium sized tumours for which ruthenium therapy generally is recommended.

Proteinases in subretinal fluid.

BACKGROUND: Degradation of the extracellular matrix by secreted proteases is connected to cell migration and proliferation in invasive growth and in scar tissue formation. In retinal detachment, retinal pigment epithelium (RPE) cells loosened from their monolayer are often seen in the subretinal fluid (SRF) and the vitreous, where they may participate in the scar tissue formation of proliferative vitreoretinopathy. To evaluate the role of SRF constituents on the release of RPE cells, we analyzed SRF in patients with retinal detachment for the presence of enzymes able to degrade extracellular matrix. METHODS: SRF was collected altogether from 16 patients undergoing retinal reattachment surgery and analyzed for activities against some of the key enzymes in extracellular proteolysis, namely collagenases, gelatinases, elastase and cathepsin G. RESULTS: Seventy-two-kilodalton gelatinase was found in all SRF samples studied, whereas the neutrophil-type 92-kDa gelatinase could not be detected. Low collagenase, elastase and cathepsin G activities could also be detected in some samples. CONCLUSIONS: The predominant type of matrix metalloproteinase present in SRF is the 72-kDa MMP-2. The proteolytic activity in SRF may be connected to the release of RPE cells into SRF and to degradation of components of the vitreous exposed to SRF.

Visual outcome of eyes with malignant melanoma of the uvea after ruthenium plaque radiotherapy.

BACKGROUND AND OBJECTIVE: To analyze the overall visual outcome in 100 consecutive eyes with malignant uveal melanoma irradiated with ruthenium-106 plaques between 1981 and 1991. PATIENTS AND METHODS: The follow-up ranged from 4 months to 10.1 years (median 3.0 years). Scattergrams of equal follow-up periods, life-table survival analysis, and Cox's proportional hazards analysis were used to analyze visual outcome. RESULTS: VA increased for some time in 14 eyes. By 3 years, VA of at least 20/70, 20/200, counting fingers, and light perception were retained in 27%, 41%, 67% and 82% of eyes, respectively. Macular pathology cause loss of reading vision; neovascular glaucoma or enucleation caused loss of light perception. In univariate analysis, large tumor size (height > 5 mm or TNM class T3) predicted visual loss of all VA levels. For the loss of light perception, the tumor's largest basal diameter > 15 mm reached significance. In Cox's multivariate analysis tumor height > 5 mm was the only significant independent risk indicator for loss of VA levels 20/70 and 20/200. For the level CF, largest basal tumor diameter also reached significance, but location of the tumor within 1 disc diameter of the optic disc, either alone or in addition to the fovea, had the greatest risk ratio (6.3, 95% CI 4.1-9.8). For losing light perception, large TNM size (T3) was the strongest risk indicator (risk ratio 10.0; 95% CI 4.5-22.5), followed by proximity of the tumor to the optic disc (risk ratio 4.3, 95% CI 2.4-7.8). CONCLUSION: Ruthenium brachytherapy may retain vision in an eye with a malignant melanoma of the uvea for a considerable period of time. The data presented are useful in patient counseling and allow comparison to subsequent series.

Dislocated nuclear fragments after cataract surgery.

Posterior nuclear dislocation is a serious complication of cataract surgery, especially when using the phacoemulsification technique. So far, there have been only a few reports concerning the indications and timing of vitrectomy with nuclear removal as well as long-term visual outcome of these eyes. We analysed 23 consecutive patients (follow-up at least 3 months) with intravitreal nuclear remnants after cataract surgery treated with vitrectomy and removal of posteriorly dislocated nuclei. All the eyes had increased intraocular pressure pre-vitrectomy, 63% had corneal oedema, 67% marked uveitis and 26% either retinal tear or detachment. Vitrectomy was performed within 1 week in 70% of eyes. In 14 eyes (61%) the final visual acuity was 20/40 or more. The main reason for poor visual outcome was retinal detachment (9%). These results indicate that with vitrectomy and removal of the nucleus good visual results can be achieved in a large proportion of eyes with posterior dislocation of nuclear remnants.

Survival of patients and metastatic and local recurrent tumor growth in malignant melanoma of the uvea after ruthenium plaque radiotherapy.

A series of 100 consecutive patients treated by ruthenium plaque radiotherapy for uveal malignant melanoma from 1981 to 1991 was studied to evaluate local recurrences, metastases, and melanoma-specific mortality. Follow up ranged from 1.0 to 10.1 years (mean, 3.3; median, 3.0 years). Local relapse was observed in 19 patients from 0.1 to 2.7 years (median, 0.7 years) after therapy. Six of these eyes were enucleated. The 5-year probability of local tumor control was 59%. Seven patients with local relapse developed metastasis 0 to 4.3 years (median, 1.4 years) later. Altogether, 18 patients developed metastases 0.9 to 4.6 years (median, 2.0 years) after the irradiation, and 15 of them died of melanoma 5 days to 3.3 years (median, 0.5 years) after detection of metastases. The 5-year probability of metastasis not developing was 61%. The overall 5-year survival was 78%, excluding causes other than malignant melanoma. Large tumor size and anterior tumor location, with or without ciliary body involvement, predicted poor prognosis both in terms of local growth, metastases, and melanoma-specific mortality. Local recurrent tumor growth was associated with a significant increase in metastasis but a nonsignificant increase in melanoma-specific mortality.

Radiotherapy of malignant melanoma of the uvea with I-125 seeds.

Nineteen patients with malignant uveal melanomas were treated with I-125 applicators. There were 10 males and 9 females with a median age of 61 years (range 42-76). The tumour was located in the choroid in 12 eyes and in the choroid and ciliary body in 7 eyes. The size of the tumours was 7-18 mm in maximal basal diameter (median 12), 5-16 mm in minimal basal diameter (median 10), and 5.5-15 mm in thickness (median 8.5). The volume of the tumours was 123-1890 mm3 (median 540). All tumours were classified as large (T3). For the irradiation, a computer program, which calculates three-dimensional dose distribution of I-125 seeds in gold plaques, was developed. By modifying the seed positions, activity and the orientation, patients can be treated individually. Iodine-125 emits low energy photons, ideal for intraocular tumour therapy and tissue. Extra-ocular tissue located behind the applicator can be completely shielded by a 0.5 mm gold layer. The dose at the apex of the tumour ranged from 30 to 120 Gy (median 93). The treatment time ranged from 44 to 600 h (median 235). Preliminary results are good. After a median follow-up of 6 months, the tumour growth has been arrested in all eyes and in 10 eyes the tumour has decreased in size.

Culture of retinal pigment epithelial cells from subretinal fluid.

Culture of cells from subretinal fluid (SRF) was performed using 29 SRF samples obtained at retinal reattachment surgery. Proliferating cells were found in 58.6% of the samples studied. The cells were of retinal pigment epithelial (RPE) origin, as evidenced by their brown pigmentation in primary culture and their positive immunostaining for cytokeratins 8/18. The age of the patients did not affect the proliferative capacity of the cells. Proliferating cells were present in all samples from eyes with proliferative vitreoretinopathy (PVR) of grade C1 or more. In primary culture the cells had a fibroblast-like morphology, resembling that of ordinary RPE cells exposed to the vitreous. We conclude that the SRF of many patients with PVR contains viable proliferating RPE cells and that SRF offers a new source of RPE cells for studies on the pathogenesis of PVR.

Cortisone, heparin and argon laser in the treatment of corneal neovascularization.

Chemical burns and contact lenses can induce corneal neovascularization. The pathogenic mechanisms of angiogenesis are not well understood. A heparin-cortisone combination has been shown to inhibit traumatic angiogenesis and argon laser photocoagulation has been useful in the treatment of corneal graft neovascularization. We describe three patients treated for corneal neovascularization with these methods. Tear fluid plasmin levels were also monitored. The corneal neovascularization was caused by contact lens use in two patients, and by a severe chemical burn in one patient. Subconjunctival cortisone injections proved to be efficient in the treatment of the contact lens induced corneal neovascularization. Corneal argon laser photocoagulation seemed to have an additional effect. The role of topical heparin remained unclear. The tear fluid plasmin levels were not significantly elevated.