Andrew K. Vine

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.

Ocular Complications Associated with Retrobulbar Injections

The authors describe six complications, of retrobulbar injections documented by fundus photography and fluorescein angiography. These include (1) injection of corticosteroid into the posterior ciliary arterial circulation resulting in emboli in the vasculature of the choroid and the optic nerve head; (2) injection of corticosteroid into the ophthalmic artery resulting in emboli in both the choroidal and retinal circulations; (3) presumed injection of lidocaine and air into the optic nerve sheath adjacent to the globe with extension anteriorly into the subretinal space and the space between the posterior vitreous and the internal limiting membrane; (4) occlusion of the central retinal artery without an associated retrobulbar hemorrhage; (5) trauma to and partial injection of lidocaine in the central retinal artery with embolization into the retinal circulation; and (6) presumed injection of lidocaine into the optic nerve sheath producing a combined central retinal vein and artery occlusion. Alternative techniques that might decrease the incidence of complications associated with retrobulbar injections are discussed.

Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease.

Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease (GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q (236–240 cM in the Marshfield genetic map), 5p (40–50 cM), and 9q (111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.

Geographic Atrophy of the Retinal Pigment Epithelium

We followed the clinical course of 29 eyes with geographic atrophy of the retinal pigment epithelium and identified three phases of the disease through which the eyes progressively evolved. In the initial phase, eyes showed focal discrete areas of atrophy of the retinal pigment epithelium in the parafoveal area. These eyes retained good visual acuity for many years. The second phase was characterized by foveal involvement in which there was a precipitous loss in visual acuity. Foveal involvement included coarse foveal granularity, thinning of the foveal retinal pigment epithelium, increasing encirclement of the fovea with focal areas of atrophy, and minimal macular drusen. The end stage of the disease was a confluent, usually circular, area of atrophy that involved the entire central macula.

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.

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.

Hydroxychloroquine Therapy in Massive Total Doses Without Retinal Toxicity

To assess the relationship between hydroxychloroquine retinal toxicity and total dose, we selectively reviewed the histories of patients who had received an additive dose exceeding 1,000 g. No retinopathy was found in nine patients treated with massive total hydroxychloroquine doses ranging from 1,054 to 3,923 g. Eight of these patients were taking recommended daily doses of 400 mg/day or less and showed no evidence of toxicity. The remaining patient treated with 600 mg/day showed evidence of preretinopathy in one eye.

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.

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 patients 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 patients 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.

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.