Alan E. Kimura

Visual Prognosis of Multifocal Choroiditis, Punctate Inner Choroidopathy, and the Diffuse Subretinal Fibrosis Syndrome

PURPOSE To characterize the visual prognosis of patients with multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), and the diffuse subretinal fibrosis (DSF) syndrome. METHODS Forty-one patients with MCP, 16 with PIC, and 5 with DSF syndrome were evaluated. The mean follow-up was approximately 39 months for patients with MCP, 51 months for patients with PIC, and 59 months for patients with DSF syndrome. Complete ophthalmic examinations were performed, and photofiles were reviewed. RESULTS The final average visual acuity for patients with MCP was 20/50. Forty-five of the 68 involved eyes (66%) had 20/40 visual acuity or better. Choroidal neovascularization (CNV) developed within choroiditis lesions in 22 (19 patients) of 68 eyes, causing visual acuity poorer than 20/50 in 14 eyes. The final average visual acuity in patients with PIC was 20/39; 23 (77%) of the 30 involved eyes had visual acuity of 20/40 or better. Six of the seven eyes with 20/50 or poorer vision had CNV. Six other eyes had CNV within the macula that regressed spontaneously with good resultant vision. Seven of the ten involved eyes with DSF syndrome had 20/200 or poorer vision. Poor vision was due to fibrosis and atrophy within the macula. CONCLUSION Most patients with MCP and PIC retained visual acuity of 20/40 or better. In nearly one third of patients with MCP and PIC, CNV developed. Severe visual loss in these diseases was usually due to subfoveal CNV. Patients with DSF syndrome had a poor prognosis due to fibrosis and atrophy involving the macula.

Differentiation of ischemic from non-ischemic central retinal vein occlusion during the early acute phase

We investigated prospectively in 128 patients (140 eyes) the role of six routine clinical tests in the differentiation of ischemic central retinal vein occlusion (CRVO) from non-ischemic CRVO during its early acute phase. There were fourfunctional tests [visual acuity, visual fields, relative afferent pupillary defect (RAPID), electroretinography (ERG)] and twomorphologic tests (ophthalmoscopy and fluorescein fundus angiography). We found that none of the six tests had 100% sensitivity and specificity in such a differentiation during the early, acute phase, so that no one test can be considered a “gold standard”; however, combined information from all six is almost always reliable. Overall, the four functional tests proved far superior to the two morphologic tests in differentiating ischemic from non-ischemic CRVO: RAPID was most reliable in uniocular CRVO (with a normal fellow eye), followed closely by ERG in all cases; combined information from RAPID and ERG differentiated 97% of cases; perimetry was the next most reliable, followed by visual acuity. The two morphologic tests performed worst; fluorescein angiography provided either no information at all on retinal capillary nonperfusion (in at least one-third of the eyes during the early, acute phase) because of multiple limitations, or sometimes provided misleading information. Ophthalmoscopic appearance is the least reliable, most misleading parameter.

Enlarged Blind Spots in Chonoretinal Inflammatory Disorders

PURPOSE This study was undertaken to better characterize patients with multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), multiple evanescent white dot syndrome (MEWDS), and diffuse subretinal fibrosis syndrome. The specific aim was to determine whether these disorders were different entities or part of a spectrum of diseases with similar features. METHODS Seventy-nine patients were included in this study. Most of the patients have been followed up prospectively since July 1980 with some found retrospectively. RESULTS Forty-one patients had MCP, 16 had PIC, 6 had diffuse subretinal fibrosis syndrome, and 16 had MEWDS. Patients with MCP had visual loss and visual field defects caused directly by visible lesions or recurrent inflammation around old lesions. In particular, clustering of lesions around the optic nerve and nasal periphery was seen in patients with MCP and appeared to be related to visual field loss. Patients with PIC also had enlarged blind spot and other field defects explained by fundus lesions. Patients with PIC and MCP did not have recurrent lesions on extended follow-up. Patients with diffuse subretinal fibrosis syndrome represented a subset of patients characterized with lesions in the posterior pole, sever scarring, and visual loss. Patients with MEWDS had the least inflammation with symmetrically distributed lesions. Minimal permanent chorioretinal scarring was seen in patients with MEWDS. Visual field defects improved in most patients with MEWDS and PIC, whereas most patients with MCP and diffuse subretinal fibrosis syndrome did not improve. CONCLUSIONS Although enlarged blind spots are a feature of all four disorders, other clinical, angiographic, and electroretinographic evidence suggest that these are different entities.

The Use Of Intravttreal Tissue Plasminogen Activator In The Treatment Of Experimental Subretinal Hemorrhage In The Pig Model

Purpose To clinically and surgically evaluate clot lysis in an animal model of subretinal hemorrhage after intravitreal injection of tissue plasminogen activator. Methods Autologous subretinal hemorrhages were created via a transvitreal approach in 18 pigs. The next day (day 1) animals were randomly selected to receive either an intravitreal injection of 0.1 mL balanced salt solution or 0.1 mL tissue plasminogen activator (25 μg) followed by observation or vitrectomy a day later. On day 2, six pigs (all treated with tissue plasminogen activator) underwent a vitrectomy in which aspiration of the subretinal hemorrhage was attempted. The other eyes were evaluated for clot lysis by ophthalmos-copy at days 3, 10, and 30. All eyes were examined histopathologically. Results The eyes that had been treated with tissue plasminogen activator demonstrated a color change at the peripheral margin, which suggested that clot lysis had occurred. At the time of the vitrectomy, the clots were liquefied partially; removal by aspiration alone, however, was not possible. Photoreceptor damage was moderate to severe by day 10 in all eyes, whether they were treated with tissue plasminogen activator or balanced salt solution. All eyes that underwent vitrectomy had moderate to severe photoreceptor damage. Conclusions In this animal model, intravitreal tissue plasminogen activator was associated with features that suggested partial clot lysis; tissue plasminogen activator did -not- produce sufficient lysis to allow surgical removal by aspiration alone, however.

Visual outcome following subretinal hemorrhage in Best disease.

Purpose To review cases of Best disease associated with subretinal hemorrhage to better understand their long-term visual prognosis. Subject and Methods Patients were identified through the photographic file database at the University of Iowa. Seventy-eight files of patients with clinical evidence of Best disease were reviewed and 12 patients (14 eyes) were identified with subretinal hemorrhage. The visual acuity and clinical course were reviewed in all of these patients when possible. Three patients demonstrated subretinal hemorrhage on their last follow-up visit. Nine patients (11 eyes) were followed through to resolution of subretinal hemorrhage. Eight patients were screened on the VMD2 gene and all were found to have disease-causing sequence variations. Results All patients noted visual loss at presentation with subretinal hemorrhage (median 20/100; range 20/30–20/400). The median final visual acuity in the 11 eyes with follow-up was 20/50 (20/16–20/400 range). Ten of 11 eyes demonstrated improvement of vision with 9/11 having a final visual acuity of 20/50 or better. Conclusion The natural history of patients with Best disease with subretinal hemorrhage and moderate visual loss is relatively good. The presence of subretinal hemorrhage in Best disease may be related to mild, incidental trauma.

Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy

Twenty-eight of 61 members of a six-generation family are affected by an autosomal dominant eye disease which has not been described previously. Affected patients are asymptomatic in early adulthood, but have vitreous cells and the selective loss of the b-wave on the electroretinogram. Later, peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata or occasionally neovascularization of the optic disc develop. Cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma can cause profound visual loss. Vitrectomy reduces traction on the retina and allows for retinal reattachment. The role of argon laser photocoagulation or cryopexy in reducing the neovascular complications remains uncertain.

Clinical and electroretinographic findings of female carriers and affected males in a progressive X-linked cone-rod dystrophy (COD-1) pedigree.

OBJECTIVE To study the clinical and electroretinographic findings of affected males and female carriers in a family with X-linked cone-rod dystrophy (COD-1). DESIGN Observational case series. PARTICIPANTS Twenty-five members of a five-generation pedigree were examined. METHODS A history of visual impairment including age at onset, loss of acuity, color vision abnormalities, photophobia, and nyctalopia was obtained. A complete ophthalmologic examination was performed, including kinetic perimetry with a Goldmann perimeter, FM 100-hue testing, and standardized Ganzfeld electroretinography following the ISCEV protocol. MAIN OUTCOME MEASURES Patients were classified as affected or unaffected on the basis of the clinical examination. All carrier females had affected sons. RESULTS Nine affected males and seven female carriers were identified. Affected males noted decreased visual acuity and poor color vision within the first two decades of life. Early in the disease, macular retinal pigment epithelial (RPE) changes were found that progressed to an atrophic macular scar by the fifth decade. Evidence of progression from macular pigment mottling to an atrophic macular lesion over a 13-year period was identified in one patient. The photopic, single-flash, b-wave amplitude was low in all affected males and declined with age. The 30-Hz flicker b-wave implicit times were abnormally prolonged in all affected males. Female carriers were asymptomatic although three had slightly abnormal color vision and small paracentral field defects and subtle RPE defects were found in three carriers. Carriers demonstrated prolongation of the 30-Hz flicker b-wave implicit time and interocular asymmetry. Five of seven carriers and two affected males demonstrated reduced oscillatory potentials and an abnormal-appearing flattened photopic a-wave. Five men and two women demonstrated a characteristic tapetal-like retinal sheen. CONCLUSIONS Affected patients in this pedigree demonstrate early loss of visual acuity and poor cone function with late rod involvement. Female carriers may appear clinically normal or may be identified by subtle color vision defects, fundus abnormalities, prolongation of the 30-Hz flicker implicit time with interocular asymmetry, or an abnormal flattened photopic a-wave. Genetic linkage analysis of this family was recently reported and the disease-causing gene has been mapped to an approximately 1-Mb interval on chromosome Xp11.4.

Acute Promyelocytic Infiltration of the Optic Nerve Treated by Oral Trans-retinoic Acid

BACKGROUND Oral trans-retinoic acid has recently been shown to be an effective treatment modality for acute promyelocytic leukemia. This type of drug differs from traditional tumoricidal agents by promoting differentiation of the malignant, immature cells. METHODS The authors describe a patient with optic nerve infiltration by acute promyelocytic leukemia documented ophthalmoscopically and confirmed by standardized echography and magnetic resonance imaging. High-resolution chromosome banding revealed the patient had a 15;17 chromosomal translocation known to be associated with acute promyelocytic leukemia. Treatment was instituted with oral all trans-retinoic acid without adjuvant radiotherapy or intrathecal chemotherapy. RESULTS Results of serial bone marrow examination showed progressive differentiation of malignant cells with complete bone marrow remission. Results of serial ophthalmic examinations showed complete resolution of the leukemic optic nerve head infiltration. CONCLUSION All trans-retinoic acid alone can be an effective treatment for optic nerve head infiltration in acute promyelocytic leukemia. This case suggests that radiation therapy may not be necessary in acute promyelocytic leukemia with optic nerve infiltration.

Linkage analysis of X-linked cone-rod dystrophy : Localization to Xp11.4 and definition of a locus distinct from RP2 and RP3

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.

The Treatment of Serous Macular Detachment Secondary 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 Bruchs membrane at the original site of focal treatment. This eye was enucleated, and results of histopathologic examination showed a choroidal melanoma.