Choroidal hemangioma treated with photodynamic therapy using verteporfin.

OBJECTIVE: To describe a new treatment for vision loss caused by subretinal fluid associated with circumscribed choroidal hemangioma. METHODS: Three patients were treated with photodynamic therapy using verteporfin for injection (Visudyne; QLT Phototherapeutics Inc, Vancouver, British Columbia). All patients had pretreatment and posttreatment fluorescein angiography and ultrasonography. Treatment parameters used were verteporfin, 6 mg/m(2), and laser light at 689 nm delivered at 50 J/cm(2) with an intensity of 600 mW/cm(2) for 83 seconds. RESULTS: All patients had complete resolution of subretinal fluid within 2 weeks of treatment. Fluorescein angiography performed 2 to 4 weeks after treatment showed absence of tumor leakage. All eyes had reduced tumor thickness or complete flattening. Visual acuity was improved in each eye. Average follow-up was 5.3 months. No complications were noted. CONCLUSION: Photodynamic therapy with verteporfin is effective in eliminating subretinal fluid and improving vision in patients with circumscribed choroidal hemangioma.

Repair of late retinal detachment after successful treatment of retinoblastoma.

PURPOSE: To analyze the results of vitreous surgery for late retinal detachment (RD) after successful treatment of retinoblastoma. METHODS: The records of all patients with retinoblastoma seen at a single ocular oncology service between 1982 and 1998 were reviewed to identify patients treated for late RD. Previous treatments, characteristics of the RD, surgical techniques used, and visual and anatomic results of the surgery were recorded. RESULTS: Of more than 500 charts reviewed, four patients treated for late RD were identified. All four had received previous, whole-eye, external beam radiotherapy and subsequently required cataract surgery. Other previous treatments included radioactive plaque, cryotherapy, xenon photocoagulation, and chemotherapy. At presentation, some patients had shifting subretinal fluid. None had a tear identifiable preoperatively, but two patients had a definite small slit tear at a tumor edge identified at surgery. One patient had a primary scleral buckle that failed. All patients had vitreous surgery with silicone oil. Average postsurgical follow-up was 30 months. Preoperative visual acuity ranged from 20/80 to light perception and improved postoperatively in two patients. The retina remained completely attached in three patients. CONCLUSIONS: Despite shifting subretinal fluid and no identifiable tear, a rhegmatogenous RD should be considered if it occurs late in patients with otherwise stable, treated retinoblastoma. Tumor reactivation must be excluded carefully. Vitreous surgery can be used to repair the RD successfully and improve vision.

Treatment of retinoblastoma vitreous base seeding.

OBJECTIVE: The purpose of the study is to describe results of a new treatment for retinoblastoma vitreous base seeding. DESIGN: The study design was a retrospective review of patients treated at an ocular oncology referral center. PARTICIPANTS: Five eyes of five patients with vitreous base seeding that occurred after previous external beam radiation therapy were treated between October 1987 and December 1994. INTERVENTION: A customized plaque made from iridium-192/platinum wire was placed to deliver 4000 cGy to the tumor apex along its entire length and systemic chemotherapy (consisting of carboplatin, vincristine, and etoposide) was given. MAIN OUTCOME MEASURES: Eye preservation and tumor control were measured. RESULTS: Vitreous base seeding was controlled completely and the eye preserved in four of the five treated eyes with an average follow-up of 26.2 months. CONCLUSIONS: The combination of a customized iridium-192 plaque and systemic chemotherapy is an effective means of treating vitreous base seeding of retinoblastoma.

Choroidal hemangiomas: visual and anatomic results of treatment by photocoagulation or radiation therapy.

PURPOSE: Choroidal hemangioma is a benign hamartoma that causes accumulation of subretinal fluid and resultant visual loss. Although photocoagulation can result in resolution of subretinal fluid, some have found that recurrence is common and final visual acuity often is poor. The purpose of this study is to evaluate the visual and anatomic results of radiation therapy and photocoagulation in treating patients with visual loss from choroidal hemangiomas. METHODS: A retrospective review was performed of patients with circumscribed choroidal hemangiomas (CCH) or diffuse choroidal hemangiomas (DCH) treated for visual loss caused by accumulation of subretinal fluid. Of 23 patients with CCH, 13 were treated by photocoagulation, 8 by plaque brachytherapy, and 2 by lens-sparing external beam radiation therapy (LSRT). All five patients with DCH were treated by LSRT. RESULTS: Of patients with CCH treated by brachytherapy, six (75%) of eight had visual acuity of 6/12 or better at 1 year and 8 (100%) of 8 had no subretinal fluid. Of patients with CCH treated by photocoagulation, 5 (38%) of 13 had visual acuity of 6/12 or better at 1 year and 6 (46%) of 13 had no subretinal fluid. Of patients with CCH treated by LSRT, none of two had visual acuity of 6/12 or better at 1 year and one of two had no subretinal fluid. Of the five patients with DCH treated by LSRT, all had complete resolution of subretinal fluid. Two had marked visual improvement and in the other three, vision was stabilized. CONCLUSIONS: Plaque brachytherapy is an effective alternative to photocoagulation for treatment of subretinal fluid caused by CCH. Lens-sparing external beam radiation therapy is effective treatment in patients with DCH.

Polymerase chain reaction detection and clinical significance of varicella-zoster virus in cerebrospinal fluid from human immunodeficiency virus-infected patients.

Varicella-zoster virus (VZV) causes ocular and other central nervous system (CNS) disease in human immunodeficiency virus (HIV)-infected persons. To study the prevalence of CNS disease due to VZV, cerebrospinal fluid (CSF) specimens from 84 consecutive HIV-infected patients with new neurologic symptoms were tested for VZV DNA by a polymerase chain reaction (PCR) assay. Six patients were PCR-positive for VZV in CSF; 3 additional patients were subsequently identified who were not part of the serial population sample. Among these 9 patients, all had clinical presentations consistent with ocular and other CNS disease due to VZV; 4 were without zoster on presentation. Sustained improvement in association with antiviral therapy was observed in 3. Therefore, VZV DNA was detected in the CSF of 7% of HIV-infected patients presenting with neurologic symptoms; the diagnosis of VZV-related CNS disease was facilitated by this assay; improvement in association with antiviral therapy was observed in some patients.

Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia.

PURPOSE: To evaluate the efficacy of topical mitomycin C in treating conjunctival and corneal epithelial dysplasia and neoplasia. METHODS: Seven eyes of seven patients with conjunctival and corneal epithelial dysplasia and neoplasia were treated with one drop of topical mitomycin C 0.04% four times a day for 7 days in alternate weeks. The patients' charts were reviewed retrospectively. Patients with either multiple recurrences or extensive ocular surface involvement were treated. In all eyes, the diagnosis of epithelial dysplasia or neoplasia was confirmed by histopathology before the onset of therapy. Patients were examined at least every 14 days during treatment and examined at intervals after completion of treatment. RESULTS: With topical mitomycin C, six eyes of seven patients had complete clinical regression of their conjunctival and corneal epithelial dysplasia and neoplasia. One eye of one patient had partial clinical regression of conjunctival and corneal epithelial dysplasia. Follow-up after completion of topical mitomycin C therapy and excision of residual disease ranged from 2 to 16 months (mean, 9 months; SD, 4.3 months) and was without clinical sign of recurrence. Topical mitomycin C therapy was associated with transitory ocular discomfort, conjunctival injection, tearing, photophobia, and punctate epithelial keratopathy. CONCLUSION: In this small series of eyes, topical mitomycin C was effective as a treatment for conjunctival and corneal epithelial dysplasia and neoplasia.

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma.

OBJECTIVE: To determine the visual anatomical results and survival after combined chemotherapy and whole eye radiotherapy for patients with bilateral Reese-Ellsworth group V retinoblastoma. SETTING: A national referral center for retinoblastoma. PATIENTS: Fourteen patients with bilateral Reese-Ellsworth group V retinoblastoma seen between March 1, 1989, and April 30, 1995, were treated. INTERVENTIONS: Patients were treated with chemotherapy (using carboplatin, etoposide, and vincristine) and whole eye radiotherapy (40-44 Gy in 20-22 equivalent fractions). A medical record review was performed to determine outcomes. MAIN OUTCOME MEASURES: Survival, eye preservation rate, and visual acuity. RESULTS: Two patients died, 1 from a primitive neuroectodermal tumor and the other from the meningeal spread of retinoblastoma. Four eyes were enucleated primarily because of severe disease at presentation. Of the remaining 20 eyes, 6 required enucleation. The disease recurred in 4 of those patients, and neovascular glaucoma developed in 2 patients. Of the 12 surviving children, 5 have a visual acuity better than l/60 in at least 1 eye. CONCLUSION: Although most of the treated group V eyes could be salvaged with chemotherapy plus radiotherapy, the resultant visual acuity was often poor.

Clinicopathologic correlation of surgically removed macular hole opercula.

PURPOSE: To determine the ultrastructural characteristic of the operculum associated with macular holes. METHODS: We developed instrumentation and a technique to capture the operculum observed with macular holes. Two opercula were studied by transmission electron microscopy. RESULTS: The two specimens were attached to a layer of native collagen identified as cortical vitreous and were composed primarily of Mueller cells and fibrous astrocytes without adjacent inner limiting membrane. No distinct retinal neuronal tissue was present. CONCLUSIONS: Our findings indicate that proliferation of fibrous astrocytes and Mueller cells occurs with the formation of a macular hole, that this reparative tissue may be dislodged, and it is the reparative tissue that previously has been interpreted as an operculum.

Inferior peripheral iridectomy in patients receiving silicone oil. Rates of postoperative closure and effect on oil position.

BACKGROUND: Silicone oil tamponade is used in treating retinal detachments, but silicone-associated complications remain frequent. Keratopathy and acute pupillary block glaucoma are related to migration of silicone oil into the anterior chamber. Since 1985, many surgeons have created an inferior peripheral iridectomy (PI) at the time of surgery to prevent forward migration of the oil, but the rate of postoperative closure of the PI and the effect on oil position have not been well defined. METHODS: The charts of 292 patients undergoing silicone oil surgery were reviewed. The status of the PI and the oil position were determined throughout the postoperative period. RESULTS: Postoperative closure of the PI occurred in 40 (33%) of 121 aphakic eyes in the early postoperative period. Forward migration of the oil was highly associated with closure of the PI (32/40, 80%). Conversely, forward oil migration occurred in only 11% (9/81) of eyes with patent PIs. The rate of PI closure was significantly greater for patients with proliferative diabetic retinopathy (21/40, 52%) than for patients with proliferative vitreoretinopathy (11/58, 19%). CONCLUSION: Postoperative closure of the PI occurred in a significant fraction of eyes undergoing silicone oil surgery, was highly correlated with forward oil migration, and occurred most frequently in eyes with proliferative diabetic retinopathy.

Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin.

PURPOSE: To investigate photoreceptor dysfunction caused by digoxin toxicity. METHODS: First, a patient who experienced toxic side effects from digoxin was studied acutely by serial electroretinography and later during convalescence. Second, the light responses of isolated photoreceptors exposed to varying amounts of digoxin were studied in vitro. RESULTS: Electroretinographic amplitudes were reduced and implicit times were delayed when digoxin levels were elevated and recovered slowly after return to normal digoxin levels. Isolated photoreceptors exhibited concentration-dependent reductions in the magnitude of the light response during digoxin exposure, suggesting reduction in the dark current due to blockade of the sodium-potassium-adenosine triphosphatase pump. Cones were about 50-fold more sensitive than rods. CONCLUSIONS: Reversible rod and cone dysfunction occur during exposure to toxic levels of digoxin. Photoreceptor dysfunction is probably due to the diminution of the dark current in response to the sodium-potassium-adenosine triphosphatase blockade.

Clinicopathologic correlation of a macular hole treated by cortical vitreous peeling and gas tamponade.

PURPOSE: To study the histopathology of a stage III macular hole that had been treated by vitrectomy with cortical vitreous and epicortical vitreous membrane peeling and gas tamponade. METHODS: The light and electron microscopic features of a treated macular hole were studied. RESULTS: A 16-microns-wide break was present in the external limiting membrane. This was sealed by Müller cell processes. Photoreceptors adjacent to the healed defect appeared normal. No cystoid macular edema was present. CONCLUSION: Cortical vitreous peeling and gas tamponade can allow the macular hole to settle and the edges to re-approximate. The residual defect can be sealed by Müller cells.

Olivopontocerebellar atrophy with retinal degeneration. Fundus characteristics and diagnostic MRI findings.

Olivopontocerebellar atrophy with retinal degeneration (OPCA type III) and autosomal dominant cerebellar atrophy of late onset (type II) appear to represent the same disease which is characterized by dominantly inherited cerebellar ataxia and pigmentary retinal degeneration. In June, 1988, a 15-year-old girl presented with objective visual acuity loss but no other findings. When seen again in January, 1991, macular changes were noted. At this time, her mother, diagnosed with multiple sclerosis, was examined and found to have atrophic macular lesions and poor vision. A brain MRI was performed which showed findings diagnostic of OPCA type III, including cerebellar and pontine atrophy and specific loss of the inferior olives. Fundus features, electroretinographic results and other clinical findings in OPCA type III are discussed and diagnostic MRI lesions are demonstrated.

Human papillomavirus in primary epithelial tumors of the lacrimal sac.

BACKGROUND: The lacrimal sac epithelium can give rise to benign and malignant neoplasms. Human papillomavirus (HPV) infection is known to be causal in the development of epithelial neoplasias elsewhere in the body. The authors have examined primary lacrimal sac tumors for the presence of HPV. METHODS: Nine primary lacrimal sac tumors (3 benign papillomas and 6 carcinomas) submitted to the Eye Pathology Laboratories at the Wilmer Institute between 1960 and 1991 were examined for the presence of HPV sequences by in situ hybridization and the polymerase chain reaction (PCR). RESULTS: Of the nine tumors, only six were suitable for analysis by PCR or in situ hybridization. All three papillomas were positive for HPV type 11. Three of the carcinomas were positive for HPV sequences, and one case could be further characterized as HPV type 18. CONCLUSIONS: Human papillomaviruses appear to be involved in the genesis of both benign and malignant neoplasms of the lacrimal sac epithelium. As in the genital tract, HPV type 11 is associated with benign lesions, whereas HPV type 18 is associated with malignancy.

Intraocular tumor suppression of retinoblastoma gene-reconstituted retinoblastoma cells.

Human retinoblastoma is caused by mutational inactivation of the retinoblastoma suppressor gene (RB). We have examined intraocular tumorigenicity of retinoblastoma cells in which RB expression was achieved by retroviral transduction. Retinoblastoma cells were injected into the anterior chambers of severe combined immunodeficient mouse eyes, and tumorigenicity was assessed. RB-expressing retinoblastoma cells usually failed to form progressive tumors in the anterior chamber, whereas the parental, RB-negative line, WERI-Rb27, was rapidly tumorigenic. These results support the hypothesis that inactivation of the RB gene is critical for the growth of retinoblastoma tumors. The potential use of RB reconstitution for treating human retinoblastoma is suggested by our finding that intraocular tumor growth can be suppressed by RB expression.

Retinoblastoma cell lines Y79, RB355 and WERI-Rb27 are genetically related.

Genesis of the childhood ocular tumor retinoblastoma results from the mutational inactivation of a single gene, RB, located on chromosome 13. Cultured cells or cell lines derived from retinoblastomas have been extensively studied for insight into mutational mechanisms of RB inactivation, functional properties of wild-type RB alleles, and pathways of retinal differentiation. Three such cell lines (Y79, RB355 and WERI-Rb27) were previously shown to have similar, heterozygous rearrangements of their RB genes, suggesting a common mutational mechanism affecting a specific region of the gene. This proposal was based on the premise that all three mutations occurred independently. By using molecular analyses of human genetic polymorphisms, we now show that these three cell lines are in fact genetically related, despite their different origins, morphologies, growth characteristics, and karyotypes. Interpretation of these and other published data suggest that both RB355 and WERI-Rb27 are probably sublines of Y79.

Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma.

Mutational inactivation of the retinoblastoma gene (RB) is found in all retinoblastomas and in a subset of other human neoplasms, including sarcomas of bone or soft tissue and carcinomas of lung or breast. Exogenous copies of wild-type RB have been shown to suppress the tumorigenicity of several types of tumor cells with endogenous RB mutations, including a previously described human prostatic carcinoma cell line. To further support a role for RB inactivation in the genesis of prostate cancer, seven primary or metastatic prostate carcinoma specimens were examined for evidence of RB mutation. By the use of immunoblot analysis and immunostaining of histologic sections, RB-encoded protein was readily detected in tumor cells of five specimens, was equivocally detected in one specimen, and was apparently absent from tumor cells of one specimen. RB mutations in the latter case were precisely characterized as (i) a deletion of 103 nucleotides containing transcriptional start sites and (ii) loss of the second RB allele. The 103-base-pair deletion was sufficient to abolish the promoter activity of upstream DNA sequences in a heterologous expression system. These results (i) demonstrate that RB can be inactivated in vivo by mutation of its promoter, (ii) confirm the existence of RB mutations in some human prostate carcinomas, and (iii) suggest the use of immunohistochemical methods to screen for RB mutations in clinical samples of common adult neoplasms.

Visual acuity loss in retinitis pigmentosa. Relationship to visual field loss.

We compared visual acuity with visual field radius in 235 patients with typical retinitis pigmentosa and no evidence of other visual acuity-limiting problems (such as cataract or foveal cystoid edema). Results show a strong relationship between visual acuity loss and proximity to the fovea of the visual field border (shortest distance from the foveal center to the border of the V-4-e isopter) for these patients. Ninety-six percent of patients with central visual field radii greater than 30 degrees have visual acuities of 20/40 or better; 32% of patients with central visual field radii smaller than 10 degrees have visual acuity of 20/40 or better.