An analysis of allelic variation in the ABCA4 gene.

PURPOSE: To assess the allelic variation of the ATP-binding transporter protein (ABCA4). METHODS: A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to systematically screen this gene for sequence variations in 374 unrelated probands with a clinical diagnosis of Stargardt disease, 182 patients with age-related macular degeneration (AMD), and 96 normal subjects. RESULTS: There was no significant difference in the proportion of any single variant or class of variant between the control and AMD groups. In contrast, truncating variants, amino acid substitutions, synonymous codon changes, and intronic variants were significantly enriched in patients with Stargardt disease when compared with their presence in subjects without Stargardt disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were 2480 instances of 213 different variants in the ABCA4 gene, including 589 instances of 97 amino acid substitutions, and 45 instances of 33 truncating variants. CONCLUSIONS: Of the 97 amino acid substitutions, 11 occurred at a frequency that made them unlikely to be high-penetrance recessive disease-causing variants (HPRDCV). After accounting for variants in cis, one or more changes that were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles overall. The nucleotide diversity of the ABCA4 coding region, a collective measure of the number and prevalence of polymorphic sites in a region of DNA, was found to be 1.28, a value that is 9 to 400 times greater than that of two other macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

Adenocarcinoma of the esophagus presenting as orbital cellulitis.

A 56-year-old man was seen with signs and symptoms consistent with orbital cellulitis. Computed tomographic scan showed a localized bony defect in the sphenoid wing, on which a biopsy was performed through a lateral orbitotomy. Pathologic examination of the surgical specimen revealed mucinous adenocarcinoma, and metastatic workup revealed an extensive lower esophageal malignant neoplasm. Arch Ophthalmol. 2000;118:986-988

Description of a new mutation in rhodopsin, Pro23Ala, and comparison with electroretinographic and clinical characteristics of the Pro23His mutation.

OBJECTIVES: To report the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a proline-to-alanine mutation at codon 23 (Pro23Ala) of the rhodopsin gene and to compare this phenotype with that associated with the more common proline-to-histidine mutation at codon 23 (Pro23His). METHODS: We examined 6 patients within a single pedigree. The electroretinograms (ERGs) of 35 patients with known Pro23His mutations and of 22 healthy individuals were reviewed. Scotopic dim flash-response amplitudes, maximum combined-response amplitudes, and photopic-response amplitudes from the ERGs of these patients were plotted against age. The ERG indices of 5 individuals in the Pro23Ala family were compared with those of the patients with Pro23His mutations and of healthy individuals. Multiple linear regression was performed to evaluate the effect of age and mutation type on amplitudes. Mutation detection was performed using single-strand conformation polymorphism analysis, followed by automated DNA sequencing. RESULTS: Patients with the Pro23Ala mutation have a clinical phenotype characterized by onset of symptoms in the second to fourth decades of life, loss of superior visual field with relatively well-preserved inferior fields, and mild nyctalopia. Comparison with patients with the Pro23His mutation demonstrates statistically significant differences (P<.001) in responses to dim flash, maximum combined, and photopic responses between patients with these mutations after controlling for the effects of age. Patients with Pro23Ala mutations were less affected by ERG criteria than patients with Pro23His mutations. Patients with Pro23Ala mutations also differed significantly from healthy patients in all ERG indices examined (P<.001), after controlling for age. CONCLUSION: We describe a rare mutation in codon 23 of rhodopsin causing autosomal dominant retinitis pigmentosa. The retinal dystrophy associated with the Pro23Ala mutation is characteristically mild in presentation and course, with greater preservation of ERG amplitudes than the more prevalent Pro23His mutation. Arch Ophthalmol. 2000;118:1269-1276

Acute posterior multifocal placoid pigment epitheliopathy with corneal stromal infiltrates.

PURPOSE: To report the association of perilimbal corneal stromal infiltrates with acute posterior multifocal placoid pigment epitheliopathy. METHOD: Case report. RESULTS: A 29-year-old woman with bilateral fundus lesions typical of acute posterior multifocal placoid pigment epitheliopathy presented with peripheral corneal stromal infiltrates that resolved with fundus lesions. CONCLUSION: Corneal stromal infiltrates may be associated with characteristic fundus lesions of acute posterior multifocal placoid pigment epitheliopathy.

Myositis associated with a Baerveldt glaucoma implant.

PURPOSE: To describe a case of myositis in the presence of a Baerveldt glaucoma implant. METHOD: Case report. RESULTS: A 41-year-old black woman developed myositis after placement of a Baerveldt glaucoma implant. Echography demonstrated migration of the seton plate against the medial rectus muscle insertion. Myositis resolved after removal of the Baerveldt glaucoma implant. CONCLUSION: The Baerveldt glaucoma implant may have precipitated myositis in this patient.

Iatrogenic central retinal vein occlusion and hyperviscosity associated with high-dose intravenous immunoglobulin administration.

PURPOSE: To describe a patient with iatrogenically induced central retinal vein occlusions secondary to serum hyperviscosity from intravenous immunoglobulin administration. METHOD: Case report. RESULTS: The patient developed bilateral central retinal vein occlusions in association with high-dose intravenous immunoglobulins. The central retinal vein occlusions resolved when the immunoglobulins were withheld and serum hyperviscosity decreased. CONCLUSION: Administration of high-dose intravenous immunoglobulins can be associated with hyperviscosity syndrome manifested by central retinal vein occlusion.

Systemic small noncleaved cell lymphoma presenting as a posterior choroidal mass.

PURPOSE: To describe a patient with intraocular involvement by systemic, small noncleaved cell lymphoma. METHODS: Case report and review of the literature. RESULTS: A patient presented with a diffusely elevated choroidal mass. Systemic evaluation led to the diagnosis of unsuspected disseminated lymphoma. CONCLUSION: Small noncleaved cell lymphoma should be included in the differential diagnosis of a choroidal mass.

Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosa.

AIM: To describe the clinical characteristics and disease course of a large family with retinitis pigmentosa (RP) from an Arg135Leu change in rhodopsin. METHODS: 29 patients in this family were evaluated. Goldmann visual fields were performed on 14 affected individuals, Ganzfeld electroretinography (ERG) on eight individuals (11-56 years), and blood samples collected on 10 individuals (11-58 years). Patient visual field data were compared with previously reported patients with different rhodopsin mutations using linear regression. RESULTS: An Arg135Leu mutation was identified in rhodopsin. Distinct stages of clinical evolution were identified for this family ranging from normal, white dots, classic bone spicules and, finally, ending with extensive retinal pigment epithelium (RPE) atrophy. 9/16 patients over the age of 20 years also demonstrated marked macular atrophy. All patients who underwent full field ERG testing demonstrated non-recordable ERGs. The overall regression model comparing solid angles of visual fields from patients with rhodopsin mutations (Pro23His, Pro347Ala, Arg135Leu) shows significant effects for age (p = 0.0005), mutation (p = 0.0014), and interaction between age and mutation (p = 0.018) with an R(2) of 0.407. CONCLUSIONS: An Arg135Leu change in rhodopsin results in a severe form of RP that evolves through various fundus appearances that include white dots early in life and classic appearing RP later. This transmembrane change in rhodopsin proves to be more severe than in a family with an intradiscal change and a family with a cytoplasmic change.

Simplified insertion technique for the SI-26NB intraocular lens.

Inserting the 13 mm SI-26NB intraocular lens is a challenging task complicated by the need to tuck the modified C-configuration haptics within a folded optic. This step causes undue stress on the haptic and may result in asymmetrical distortion and subsequent decentration. Excluding this step simplifies the technique, as well as decreases the degree of acute angle stress on the haptic as it is passed through the scleral tunnel.

Optimal folding axis for acrylic intraocular lenses.

Acrylic intraocular lenses (IOLs) are easier to insert than foldable lenses of other materials. In addition to material properties, the structure of acrylic lenses allows an optimal folding angle along the 10 to 4 o'clock axis. Folding the IOL along this axis simplifies the manipulation of the leading haptic during insertion and places the trailing haptic within the capsular bag before the folded optic is released.

Optic disc vasculitis.

BACKGROUND: Our studies had indicated that optic disc vasculitis (ODV) is a distinct clinical entity. We investigated the presentation and clinical characteristics of ODV and determined the efficacy of systemic corticosteroids in its management. METHODS: From 1973 to 1997, we investigated 32 patients (34 eyes) with ODV. The information was obtained by complete medical and ophthalmic history taking and a detailed ophthalmic examination at the initial and follow-up visits. Non-parametric analysis of demographic characteristics and Cox proportional hazard modeling of treatment outcomes was performed. RESULTS: The most common presenting symptom was blurred vision (in 31/34 eyes--91.2%). Visual acuity was 6/12 or better in 82.4% and 6/30 or better in 94.1% of the eyes. All eyes had an enlarged blind spot, vitreous cells and optic disc edema. Fluorescein angiography demonstrated retinal peripapillary phlebitis in 52.6% of the eyes. Systemic hypertension in young patients (P=0.004) and frequency of smoking (P=0.004 for males, P=0.046 for females) were significantly higher than in the general population. Treatment with systemic corticosteroids improved the rate of resolution of optic disc edema and vitreous cells, reducing median resolution times (P=0.042). There was a tendency towards improved central visual fields with treatment (P=0.09). Final visual acuity was 6/12 or better in 25 (92.6%) and 6/18 or better in all of the 27 eyes followed by us. CONCLUSION: Our study indicates that our cases represent a distinct clinical entity of ODV and not just a potpourri of unilateral optic disc edema of different etiologies. It is a self-limiting disease, usually with good prognosis, and benefits from treatment with systemic corticosteroids. The presence of retinal peripapillary phlebitis on fluorescein angiography suggests mild vasculitis of the optic nerve head as the primary pathological mechanism in this disorder.

Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea.

OBJECTIVES: To evaluate the value of genotype-based dosing by polymerase chain reaction (PCR)-based polymorphism screening in terms of cost-effectiveness for treatment with azathioprine in Korea. METHODS: Decision analysis was employed to compare a genotype-based dosing strategy with the conventional weight-based dosing strategy using a hypothetical cohort composed of rheumatoid arthritis and systemic lupus erythematosus patients. The time horizon was set up as 1 yr. Direct medical costs were used. Data used were obtained from previous reports, except for PCR and admission costs, which were from real cases. Cost-effectiveness analysis was conducted from a societal perspective. Outcomes were measured as a total expected cost and an incremental cost-effective ratio. RESULTS: In the base case model, total expected cost and the probability of not dropping out owing to serious adverse events of the conventional weight-based dosing and the genotype-based dosing strategy were 1339 x 10(3) Korean won (1,117 US dollars) and 1109 x 10(3) Korean won (926 US dollars), and 97.06 and 99.90%, respectively. CONCLUSIONS: Our model suggests that a genotype-based dosing strategy through PCR-based thiopurine methyltransferase (TPMT) polymorphism screening is less costly and more effective than the conventional weight-based dosing strategy in Korea, as it was associated with a marked reduction in the number of serious adverse events.

Corneal thickness in Fuchs' dystrophy with and without epithelial oedema.

PURPOSE: To investigate whether the occurrence of epithelial oedema in Fuchs' endothelial dystrophy is associated with a particular corneal thickness or the extent of central corneal guttae. METHODS: Sixty-seven patients, aged 52-90 years, presenting in our clinic with Fuchs' dystrophy were divided on the basis of the presence or absence of epithelial oedema as determined by slit lamp examination. After exclusion of extreme cases, the 56 cases without oedema were compared with the 10 cases with oedema with respect to corneal thickness, measured by ultrasound pachymetry and corneal guttae diameter, obtained from the slit lamp examination. RESULTS: Mean corneal thickness was significantly higher (p = 0.002) in the oedematous group (mean = 0.682 mm) than in the group without epithelial oedema (mean = 0.624 mm). A corneal thickness greater than 0.650 mm was associated with a greater than 85% probability of oedema occurrence. Corneal guttae diameter did not differ significantly (p = 0.941) between the two groups and was not significantly correlated with corneal thickness (p = 0.269). CONCLUSION: There is a demonstrable association between epithelial oedema and the measured thickness of the cornea.

Multifocal electroretinography in multifocal choroiditis and the multiple evanescent white dot syndrome.

PURPOSE: To study and compare the findings on multifocal electroretinography (MERG) between multifocal choroiditis (MFC) and the multiple evanescent white dot syndrome (MEWDS). SUBJECT AND METHODS: Patients were recruited prospectively from the Department of Ophthalmology & Visual Sciences at the University of Iowa Hospitals & Clinics. They were evaluated using Goldmann visual fields (GVF) and MERG. Patients were diagnosed as having either MFC or MEWDS based on their clinical findings before MERG testing. RESULTS: Nineteen patients (23 eyes) were included in the study. Eleven patients were diagnosed with MFC and eight patients with MEWDS. Fourteen eyes with MFC and seven eyes with MEWDS were tested with MERG during the acute phase of their respective conditions. Fourteen patients (8 MFC and 6 MEWDS) were followed serially with MERG. Patients with MEWDS demonstrated focal depression corresponding to GVF defects with subsequent near total recovery of the MERG to baseline. Patients with MFC typically demonstrated diffuse loss of function over the entire test field. Focal scotomata, in addition to the diffuse depression, could be identified in 7 of 14 patients. Patients with MFC demonstrated only partial or no recovery of MERG following acute episodes, which was significantly different from the course followed by patients with MEWDS (P < 0.001, Fisher's exact test). CONCLUSION: Multifocal electroretinography differentiates MFC from MEWDS. Patients with MFC have permanent damage to the retina with diffuse depression of MERG. Patients with MEWDS, however, typically demonstrate greater focal loss initially on MERG followed by nearly full recovery of first order retinal function.

Evaluation of patients with visual field defects following macular hole surgery using multifocal electroretinography.

PURPOSE: To investigate patients with visual field defects following macular hole surgery to determine the cause of such defects, specifically with reference to ischemic damage versus mechanical trauma. METHODS: Five patients with known visual field defects following macular hole surgery were studied with Goldmann perimetry, Humphrey automated perimetry, and multifocal electroretinography (MERG). Three patients returned at a later date for nerve fiber layer analysis. RESULTS: None of the five patients demonstrated evidence of a- or b-wave loss on MERG in the regions corresponding to the visual field defects. Two of three patients studied with the nerve fiber layer analyzer demonstrated significant loss of nerve fiber layer thickness in the quadrant corresponding to the field defect. CONCLUSION: The normal MERG results indicate that the possibility of an arteriolar occlusion as the principal cause for the defects is unlikely in most cases. Data suggest that the site of damage is in the nerve fiber layer, although the specific cause of this damage remains to be determined.

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.