Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16.

OBJECTIVE: To report visual acuity during the first three years after iodine 125 (I(125)) brachytherapy for medium-sized choroidal melanoma and to identify important baseline and treatment factors associated with posttreatment visual acuity in a group of patients who were treated and observed prospectively as part of a large, randomized clinical trial. DESIGN: Observational case series within a randomized, multicenter study. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study randomized trial of I(125) brachytherapy versus enucleation had choroidal melanoma of at least 2.5 mm but no more than 10.0 mm in apical height, and no more than 16.0 mm in largest basal dimension. One thousand three hundred seventeen patients enrolled from February 1987 through July 1998; 657 patients were assigned to I(125) brachytherapy. Visual acuity data for 623 patients who received I(125) brachytherapy as randomly assigned and who have been observed for at least 1 year were analyzed for this report. METHODS: Under study protocol, an ophthalmic evaluation, including best-corrected visual acuity measurement of each eye, was performed at baseline, every 6 months thereafter for 5 years, and once yearly thereafter. Two poor vision outcomes, visual acuity of 20/200 or worse that was confirmed at the next follow-up examination and loss of six lines or more of visual acuity from baseline that was confirmed at the next follow-up examination, were analyzed to identify baseline and treatment characteristics that were associated with posttreatment visual acuity. RESULTS: At baseline, median visual acuity in the eye with choroidal melanoma was 20/32, with 70% of eyes having 20/40 or better and 10% of eyes having 20/200 or worse visual acuity. Three years after I(125) brachytherapy, median visual acuity was 20/125, with 34% having 20/40 or better and 45% having 20/200 or worse visual acuity, including eyes that were enucleated within 3 years of treatment. Life-table estimates of percentages of patients who lost six or more lines of visual acuity from baseline, a quadrupling of the minimum angle of resolution, with this finding confirmed at the next 6-month follow-up examination, were 18% by 1 year, 34% by 2 years, and 49% by 3 years after treatment. Life-table estimates of percentages of patients with baseline visual acuity better than 20/200 whose visual acuity decreased to 20/200 or worse, confirmed at the next follow-up examination, were 17% by 1 year, 33% by 2 years, and 43% by 3 years after treatment. As soon as a poor vision outcome was observed, improvement of visual acuity to a level that no longer met the definition for a poor vision outcome was rare. Greater baseline tumor apical height and shorter distance between the tumor and the foveal avascular zone (FAZ) were the factors most strongly associated with loss of six or more lines of visual acuity after treatment. These two factors and baseline visual acuity also were strongly associated with visual acuity 20/200 or worse after treatment. Patient history of diabetes, presence of tumor-associated retinal detachment, and tumors that were not dome shaped also were associated with greater risk for both of the poor vision outcomes. CONCLUSIONS: Forty-three percent to 49% of treated eyes had substantial impairment in visual acuity by 3 years after I(125) brachytherapy, defined as a loss of six or more lines of visual acuity from the pretreatment level (49% of eyes) or visual acuity of 20/200 or worse (43% of eyes) that was confirmed at the next 6-month examination. Patients with a history of diabetes and patients whose eyes had thicker tumors, tumors close to or beneath the FAZ, tumor-associated retinal detachment, or tumors that were not dome shaped were those most likely to have a poor visual acuity outcome within 3 years after I(125) brachytherapy.

Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study.

AIMS: To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO). METHODS: 15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 microg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6. RESULTS: Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed. CONCLUSION: Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.

Hyperhomocysteinemia: a risk factor for central retinal vein occlusion.

PURPOSE: Previous studies have documented that elevated plasma homocysteine level is a risk factor for vascular disease. This study was performed to determine whether hyperhomocysteinemia is a risk factor for central retinal vein occlusion. METHODS: In a case-control study, data from 74 patients with documented central retinal vein occlusion were reassessed. Control subjects consisted of individuals referred to the same clinic for assessment of a nonretinal vascular disease. Hyperhomocysteinemia was defined as a total plasma homocysteine level above the 95th percentile in the control group. RESULTS: The mean total plasma homocysteine level was 11.58 +/- 4.67 micromol/l (range, 5-26 micromol/l) for cases, and 9.49 +/- 2.65 micromol/l (range, 5-20 micromol/l) for control subjects. Of the 74 patients with a central retinal vein occlusion, 16 (21.6%) had total plasma homocysteine levels above the 95th percentile in the control group (odds ratio, 6.53; 95% confidence interval, 1.81-23.50; P =. 003). Hyperhomocysteinemia was present in five (55%) of the nine individuals with bilateral disease, nine (30%) of the 30 patients with ischemic occlusions, and 45 (31%) of the 83 eyes with severe visual loss. CONCLUSION: Hyperhomocysteinemia is a risk factor for central retinal vein occlusion and may suggest a poor prognosis in patients with central retinal vein occlusion.

Hyperhomocysteinemia: a new risk factor for central retinal vein occlusion.

PURPOSE: Previous studies have documented that an elevated plasma homocysteine level is a risk factor for vascular disease. The purpose of this study is to determine whether hyperhomocysteinemia is a risk factor for central retinal vein occlusion. METHODS: This case-controlled study involved reassessment of 74 patients with documented central retinal vein occlusion. Control subjects consisted of individuals referred to the same clinic for assessment of a nonretinal vascular disease. Hyperhomocysteinemia was defined as a total plasma homocysteine level above the 95th percentile in the control group. RESULTS: The mean total plasma homocysteine level was 11.58 mumol/L for cases and 9.49 mumol/L for controls. Of the 74 patients with a central retinal vein occlusion, 21.6% had total plasma homocysteine levels above the 95th percentile in the control group (odds ratio, 6.53; 95% confidence interval, 1.81 to 23.50, P = .003). Hyperhomocysteinemia was present in 55% of cases with bilateral disease, 30% of ischemic cases, and 31% of cases with severe visual loss. CONCLUSION: Hyperhomocysteinemia is a risk factor for central retinal vein occlusion.

Atypical, severe toxoplasmic retinochoroiditis in elderly patients.

BACKGROUND: The diagnosis of toxoplasmic retinochoroiditis is based primarily on characteristic ocular findings, with supportive serologic evidence. Clinical recognition of atypical presentations is critical for timely antiparasitic drug therapy. METHODS: Case histories were reviewed for seven presumed immunocompetent elderly patients with atypically severe (multifocal or diffuse or both) toxoplasmic retinochoroiditis. Three cases initially were misdiagnosed as acute retinal necrosis syndrome. The correct diagnosis was confirmed in each case by response to antiparasitic drug therapy, polymerase chain reaction studies of intraocular specimens, or histopathologic analysis. RESULTS: The patients ranged in age from 69 to 82 years (median, 74 years). Only three patients had intercurrent medical conditions that may be associated with subtle immune dysfunction (diabetes mellitus and hepatitis C). The extensive necrotizing retinochoroiditis in each patient was nonhemorrhagic and not associated with occlusive retinal arteritis. Despite prompt response to antiparasitic drug therapy, prolonged treatment usually was required, and four patients had retinitis reactivation after discontinuing treatment. Significant visual loss accompanied the infection in most eyes. CONCLUSION: Toxoplasmosis should be considered as a cause of multifocal or diffuse necrotizing retinitis or both in elderly patients. Older patients may be more susceptible to severe ocular Toxoplasma infections because of age-related decline in cell-mediated immunity and chronic underlying diseases.

Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study.

PURPOSE: To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS: Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS: Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS: Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.

Peripheral choroidal neovascularization.

Peripheral choroidal neovascularization can result in an elevated subretinal lesion which can simulate a choroidal tumor. We reviewed 8 eyes with 11 peripheral areas of subretinal fluid and exudate which were subsequently determined to be secondary to peripheral choroidal neovascularization. Previous reports of peripheral choroidal neovascularization have emphasized the hemorrhagic nature of these lesions which can simulate a choroidal melanoma. In contrast, turbid subretinal fluid and exudate characterized the majority of peripheral lesions in this series and the majority of these patients were referred with a diagnosis of choroidal metastasis. Clinical examination with fluorescein angiography and echography can effectively distinguish these areas of peripheral choroidal neovascularization from choroidal metastasis.

Thrombin in the management of full thickness macular holes.

PURPOSE: As thrombin is a known stimulator of retinal glial and pigment epithelial cells, we performed a pilot study to evaluate the use of thrombin as adjunctive mitogen therapy in vitreous surgery for full-thickness macular holes. METHODS: Macular hole surgery was performed on 25 eyes of 24 consecutive patients with stage II, III, or IV macular holes. After removal of the posterior hyaloid, peeling of epiretinal membranes, and fluid-air exchange, 0.05 mL or 0.1 mL of thrombin (100 units/ mL) was placed over the macular hole. After infusion of a gas tamponade, the patient's head was kept in a supine position for 1 hour, and then was kept in a prone position for approximately 2 weeks. RESULTS: Closure of the macular hole with one procedure was achieved in 80% of the eyes. Sixty-five percent of the eyes with a closed macular hole achieved a visual acuity of 20/40 or better. Postoperative inflammation was present in all eyes, and a small hypopyon developed in 28% of the eyes. CONCLUSION: Thrombin therapy failed to markedly increase the success rate of macular hole surgery.

Choroidal blastomycosis. A report of two cases.

PURPOSE: To review the presentation and course of choroidal blastomycosis, a rare chorioretinal mycotic infection, which results from disseminated blastomycosis. METHODS: Two cases of disseminated blastomycosis with ocular infection limited to the choroid are presented. Each patient was diagnosed through biopsy of skin lesions demonstrating the characteristic histologic features and the budding yeast. RESULTS: Systemic evaluation revealed extensive disseminated disease with involvement of the eye, lung, skin, bone and joint, central nervous system, and genitourinary system. Both patients were successfully treated with intravenous amphotericin B with elimination of ocular and systemic disease. CONCLUSION: Although rare, blastomycosis can result in choroidal mycotic infection in immune competent individuals. Tissue biopsy to confirm the diagnosis and extensive systemic evaluation are required.

Cytogenetic analysis of posterior uveal melanoma.

Cytogenetic analysis was performed on short-term cultures of primary tumor samples from seven patients with posterior uveal melanoma. Informative data were obtained from four patients, all of whom had a near-diploid chromosomal number and clonal chromosomal alterations. Analysis of one patient's tumor revealed monosomy 3 as the only cytogenetically distinguishable aberration. Trisomies of chromosome 8 and i(8)(q10) were detected in two other patients in combination with monosomy of chromosome 3. The fourth patient's karyotype displayed two different translocations. One translocation, der(6)t(6;8)(q12;q13.1), resulted in the over-representation of 8q13.1-->qter and a partial monosomy of 6q12-->qter; the other translocation, der(9)t(6;9)(p12;p23), produced a partial trisomy of 6p12-->pter and a partial monosomy of 9p23-->pter. These results support the view that the recurring pattern of chromosomal rearrangements in ocular melanoma is unique from that associated with cutaneous malignant melanoma. Furthermore, these results help confirm that chromosomes 3, 6, and 8 are nonrandomly altered in ocular melanoma.

The role of abnormalities in the anticoagulant and fibrinolytic systems in retinal vascular occlusions.

The hemostatic mechanisms involve both an anticoagulant system to check the coagulation cascade and a fibrinolytic system to remove formed fibrin clots. Abnormalities of the hemostatic system or acquired abnormal hematological factors can produce a thrombophilic state which accounts for 15-28% of unexplained systemic vascular thrombosis in young patients. Similar abnormalities have recently been identified in some patients with retinal vascular occlusions. Screening of selected patients with retinal vascular occlusions may reveal additional ophthalmological patients with specific thrombotic syndromes.

Candida endophthalmitis associated with intraocular lens implantation: efficacy of fluconazole therapy.

Four patients with Candida parapsilosis endophthalmitis following intraocular lens implantation were treated with oral fluconazole. All had failed prior therapy with intravitreal amphotericin B. The only patient who had the lens implant removed was cured after treatment with fluconazole for one year. Three patients who did not have the lens implant removed had resolution of symptoms and return of visual acuity towards normal during the year they were on fluconazole. However, five months after therapy had been stopped, all three had decreasing visual acuity, and in two, culture of vitreous fluid yielded C. parapsilosis. Fluconazole may be effective for treatment of endophthalmitis associated with an intraocular lens implant, but only when the implant is removed also.

Severe periphlebitis, peripheral retinal ischemia, and preretinal neovascularization in patients with multiple sclerosis.

Two patients with definite multiple sclerosis and marked retinal periphlebitis developed occlusive peripheral retinal vasculitis, which resulted in peripheral retinal ischemia and peripheral retinal neovascularization. Results of investigation for other causes of peripheral proliferative retinopathies were negative in both patients although one patient had a positive anticardiolipin antibody. Both patients have been followed up for over seven years and have maintained good visual acuity with mild regression of the preretinal neovascularization without laser intervention. An analysis of these two cases and six other reported cases indicates that severe periphlebitis can evolve into occlusive peripheral vasculitis, which results in peripheral retinal neovascularization in patients with multiple sclerosis.

Diffuse infiltrating retinoblastoma.

The authors describe two children who presented with atypical posterior uveitis and who were subsequently diagnosed as having diffuse infiltrating retinoblastoma. A review of these two cases and 26 previously published cases was performed to assess the epidemiology, presenting signs, and usefulness of diagnostic tests. In contrast to typical retinoblastoma, results of histologic analysis showed that only 4 of the 28 cases with infiltrating lesions contained calcium. Computed tomography scans and ultrasonography were not particularly helpful and many eyes required an anterior chamber paracentesis to establish the correct diagnosis. A systematic approach to the diagnosis of diffuse infiltrating retinoblastoma is presented.

Endolaser photocoagulation in penetrating and perforating intraocular foreign bodies.

Ten consecutive eyes that had undergone a pars plana vitrectomy and argon endolaser photocoagulation for penetrating or perforating posterior segment foreign bodies were reviewed. All eyes had undergone a pars plana vitrectomy plus or minus lensectomy, removal of the intraocular foreign body in those eyes with a retained foreign body, endolaser photocoagulation of posterior chorioretinal tears, and peripheral buckle for peripheral retinal pathology. Postoperatively (minimum follow-up, 6 months), all eyes had an attached retina. Eighty percent of the eyes had a visual acuity of 20/40 or better. Advantages of endolaser photocoagulation of posterior breaks include: microscopically controlled sealing of posterior tears, less destructive than posterior cryotherapy, effective when severe choroidal swelling is present, and absence of dispersion of viable retinal pigment epithelial cells which has been documented with external cryotherapy.