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.

Retinal arteriolar macroaneurysms: long-term visual outcome.

Visual outcome was analysed in 16 consecutive eyes with symptomatic retinal arteriolar macroaneurysms treated by direct laser photocoagulation and 26 consecutive symptomatic eyes followed with no treatment. No difference existed between groups in presenting visual acuity, macular involvement, presence of macular subretinal fluid, or presence or location of associated haemorrhage. The mean follow up was 41 months. In the 26 untreated eyes, visual acuity was improved by 2 or more lines in 13 (50%), was unchanged in nine (35%), and decreased in four cases (15%). In the 16 treated cases, three improved (19%), seven were unchanged (43%), and six had decreased visual acuity (38%). The average minimum angle of resolution improved 0.53 log units in untreated cases and decreased 0.14 log units in treated cases (p = 0.02). Multivariable logistic regression modelling analysis revealed that laser treatment remained a significant risk factor for final visual acuity of less than 20/80 even when controlling for the effects of subretinal haemorrhage and foveal subretinal fluid (odds ratio 8.4, p = 0.01). Laser photocoagulation directly to the macroaneurysm did not improve the visual outcome in this series.

Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q.

BACKGROUND AND OBJECTIVE: We identified a large family affected with a macular dystrophy whose main clinical features are similar to those of Stargardt's disease. Unlike true Stargardt's disease, the disorder in this family is inherited in an autosomal dominant fashion. We sought to identify the chromosomal location of the disease-causing gene and to clinically define the phenotype in a number of affected family members. METHODS: Thirty-two family members underwent clinical examination. A total of 23 affected family members were identified, and these patients were genotyped at candidate loci with short tandem repeat polymorphisms. The LINKAGE computer program was used for linkage calculations. RESULTS: Affected patients had normal vision in early childhood but began to experience difficulty with central vision between 5 and 23 years of age. Fundus examination early in the disease course revealed flecks in the macula. Central atrophy developed later, with visual acuity decreasing to 20/200 or worse in all patients older than 31 years. Fluorescein angiography revealed no evidence of choroidal silence. Electroretinograms were near normal in younger affected individuals and were most notable for prolonged implicit times in a 73-year-old patient. Chromosome linkage analysis revealed the disease-causing gene to be located near the centromere on the long arm of chromosome 6. The maximum lod score was 5.5 (theta = 0) with marker D6S280. Multipoint analysis resulted in a peak lod score of 6.2 in the interval between markers D6S313 and D6S252 and excluded the interval containing the North Carolina macular dystrophy gene. CONCLUSIONS: This autosomal dominant macular dystrophy is clinically similar to Stargardt's disease, with the exception of its pattern of inheritance. The clearly progressive nature of the disease distinguishes it from North Carolina macular dystrophy, whose causative gene is also located on the long arm of chromosome 6. Identification of the gene involved in this disease may provide clues to the pathogenesis of age-related macular degeneration.

Erosive vitreoretinopathy. A new clinical entity.

PURPOSE: Vitreoretinopathies are disorders characterized by an abnormal vitreous gel structure and associated retinal changes. The authors report a pedigree with vitreous changes characteristic of the vitreoretinopathies, but with retinal pigment epithelial changes, electroretinographic abnormalities, and a clinical course distinct from previously described entities. METHODS: Twenty-six family members were examined. Complete ophthalmologic examinations, electroretinography, and perimetry were performed on patients who were at genetic risk for the disease. Particular attention was given to vitreous morphology and examination of the retinal and retinal pigment epithelium (RPE). RESULTS: Fifteen individuals affected with an autosomal dominant vitreoretinal degeneration were identified. The disease is characterized by nyctalopia, progressive visual field loss, marked vitreous syneresis, progressive RPE atrophy, and combined traction-rhegmatogenous retinal detachments (11 patients). Thinning or "erosion" of the RPE in younger patients permits increased visualization of the choroidal vessels. In advanced conditions, equatorial areas are seen that appear clinically devoid of RPE, with extensive posterior atrophy in older patients. Diffuse rod-cone dysfunction is demonstrated by electroretinography. High myopia, epiphyseal dysplasia, orofacial anomalies, and systemic manifestations characteristic of other vitreoretinopathies are not present. CONCLUSION: The authors describe an entity clinically distinct from other vitreoretinopathies. The disease is characterized by pronounced vitreous abnormalities, complicated retinal detachments, and a progressive pigmentary retinopathy. The most unusual and constant feature is the progressive change in RPE with concurrent visual field constriction and electroretinographic abnormalities. Because the RPE initially seems normal and progressively thins or "erodes" in the equatorial periphery, the descriptive name "erosive" vitreoretinopathy is proposed.

Surgical management of melanocytoma of the ciliary body with extrascleral extension.

We treated four white women with extrascleral extension of suspected ciliary body melanomas with a modified block excision (three patients) or enucleation (one patient). Light and transmission electron microscopy established the diagnosis of ciliary body melanocytoma with extrascleral extension in each patient. Two eyes were irradiated before block excision. Block excision involved simultaneous removal of full-thickness cornea and sclera, iris, and ciliary body with tectonic corneoscleral grafting. The postoperative visual acuity of the three patients treated with a modified block excision was 20/25, 20/50, and 20/60, respectively. No patient experienced local tumor recurrence (30 to 60 months of follow-up). The two irradiated eyes eventually developed radiation-associated complications. After three years the other block excision patient had visual acuity of 20/25. Ciliary body melanocytoma should be included in the differential diagnosis of pigmented tumors of the anterior uvea with extrascleral extension. En bloc excision with simultaneous full-thickness corneoscleral resection is indicated in circumscribed ciliary body tumors, especially when extraocular extension is present.

Procollagen II gene mutation in Stickler syndrome.

Four affected members of a family with Stickler syndrome were found to have a single base-pair deletion resulting in a translational frameshift in exon 40 of the procollagen II (COL2A1) gene on chromosome 12. This mutation was not seen in any of five clinically unaffected family members or in any of 15 unrelated control patients. All affected members had distinctly abnormal vitreous syneresis and all had retinal perivascular pigmentation. Retinal detachments occurred in three of the four affected patients. Three of the four affected patients had peripheral cortical "wedge" cataracts, and the fourth had extensive nuclear sclerosis. Abnormalities of the soft palate were found in all four affected patients. All patients reported severe joint pains, and epiphyseal dysplasia was found radiographically in all patients.

Long-term visual outcome in Terson syndrome.

The presentation and long-term visual outcome in 30 eyes with Terson syndrome is evaluated. In 25 of 30 eyes (83%), visual acuity of 20/50 or better was attained. This occurred in 12 of 16 eyes (75%) managed by observation alone and 12 of 14 eyes (86%) treated by pars plana vitrectomy. The most common long-term sequelae in all eyes studied was the formation of an epiretinal membrane. These occurred in 14 of 18 eyes (78%) followed for 3 or more years but accounted for significant visual loss in only 2 eyes. There was no difference in final visual outcome between those patients undergoing vitrectomy and those managed conservatively. However, visual recovery was more rapid in eyes undergoing vitrectomy despite the fact that vitrectomy was reserved for eyes with more dense vitreous hemorrhage.

Ocular findings in Turcot syndrome (glioma-polyposis).

Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps.

Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula.

Serous detachment of the macula is a well-known complication in patients with an optic nerve pit. Despite the many descriptions of this condition and possible treatment options, the long-term natural history is not well known. The authors identified 15 eyes of 15 consecutive patients seen over 21 years who were diagnosed with a serous detachment of the macula arising from an optic nerve pit. Average length of follow-up was 9 years. Twelve eyes lost three or more lines of vision, two eyes remained unchanged, and only one eye improved. All of the 12 eyes losing three or more lines of vision experienced this decrease within the first 6 months of follow-up. Although only two patients had a visual acuity of 20/200 or less initially, 12 of 15 patients had a visual acuity of 20/200 or less at the time of their last examination. The appearance of the macula at last examination included cystic changes of the neurosensory retina, full-thickness hole formation, retinal pigment epithelial mottling, and lamellar hole formation in the outer retinal layer. The long-term visual prognosis in patients with optic nerve pit and untreated serous retinal detachment of the macula is poor, and visual loss occurs within 6 months of the serous detachment.

Pars plana vitrectomy in the management of retinal detachments associated with degenerative retinoschisis.

Pars plana vitrectomy and gas-fluid exchange were used to successfully reattach eyes of 12 patients who had symptomatic retinoschisis retinal detachments (RDs) associated with large or posterior outer-layer holes. Visual acuity improved postoperatively in seven (58%) eyes, was unchanged in two (17%) eyes, and decreased in three (25%) eyes. Loss of vision was secondary to a mild posterior subcapsular cataract in one eye and to epiretinal membranes in the other two. In two other eyes, cataracts developed that subsequently required an extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC IOL) implantation with 20/20 visual acuity in both eyes after cataract surgery. All eyes with a macula-involved RD stabilized or improved in visual acuity. Surgical indications, techniques, and results in the management of these retinoschisis RDs are discussed.

Management of siderosis bulbi due to a retained iron-containing intraocular foreign body.

The authors report their experience in managing 14 cases of siderosis bulbi secondary to a retained iron-containing intraocular foreign body (IOFB). The IOFB was removed in 12 of the 14 eyes. The IOFB was removed with a sclerotomy and external magnet (5 eyes), a pars plana vitrectomy (PPV) and intraocular forceps (5 eyes), a PPV and intraocular magnet (1 eye), and a PPV with aspiration using the suction mode of the vitrectomy instrument (1 eye). A siderotic cataract developed in 11 eyes and cataract extraction resulted in postoperative visual acuity ranging from 20/15 to 20/40. The most recent siderotic cataracts have been managed with cataract extraction and posterior chamber intraocular lens (PC IOL) implantation. No patient in this series experienced visual deterioration after receiving medical attention. The current management of siderosis bulbi is discussed.

Rural endophthalmitis.

The antibiotic regimens recommended for empiric use in posttraumatic endophthalmitis are based on data collected from medical centers in large metropolitan areas. In rural areas, trauma resulting in endophthalmitis frequently involves injuries with perforating objects that are contaminated with organic matter. These rural cases therefore may not be comparable with endophthalmitis occurring after nonrural injuries. A 10-year retrospective analysis was performed to investigate the incidence of rural endophthalmitis as well as determine the type of causative organisms. Endophthalmitis developed in 24 (30%) of 80 patients with rural penetrating trauma, compared with 23 (11%) of 204 patients with nonrural penetrating trauma. Of 24 patients, Bacillus spp were isolated in 11 (46%), followed by gram-negative rods in 7, Staphylococcus epidermidis in 6, and streptococcal species in 5. In 10 (42%) of these 24 patients with rural trauma, more than one organism was isolated. Bacillus spp were involved in six (60%) of ten of these mixed infections. Based on these findings, the authors suggest an intravitreal regimen of gentamicin along with either vancomycin or clindamycin for the empiric therapy of rural endophthalmitis.

Idiopathic premacular gliosis in children and adolescents.

We treated three patients under 20 years of age who had idiopathic premacular gliosis, a disorder found primarily in patients older than 50 years of age. Initial visual acuity ranged from 20/20 to 20/50, remained unchanged in one patient, improved in one patient, and decreased in one patient. Final visual acuity ranged from 20/15 to 20/500 with an average follow-up of 60 months (range, ten to 102 months). Included in this series is a 6-year-old boy with idiopathic premacular gliosis. Children and adolescents with idiopathic premacular gliosis may develop progressive visual loss to a level where vitrectomy should be considered.

The treatment of serous macular detachment secondary to choroidal melanomas and nevi.

The authors successfully treated with laser photocoagulation five patients who had a serous macular detachment secondary to leakage from a pigmented choroidal tumor. Three patients had dye leakage on fluorescein angiography from a choroidal neovascular membrane. The subretinal fluid resolved in all three patients after the neovascular membrane was obliterated by either krypton red (2 patients) or argon green (1 patient) laser photocoagulation. The other two patients had prominent leakage from a localized choroidal neovascular membrane as well as mild diffuse leakage over the entire tumor. Focal argon laser treatment to the neovascular membrane alone did not cause permanent resolution of the subretinal fluid. The fluid did resolve, however, after the entire area of diffuse leakage was retreated with photocoagulation. In one of the patients who received both focal and confluent laser treatment, the choroidal tumor grew in a collar-button fashion through Bruch's membrane at the original site of focal treatment. This eye was enucleated, and results of histopathologic examination showed a choroidal melanoma.