Syphilitic posterior uveitis: correlative findings and significance.

Twenty-one patients with syphilitic posterior uveitis were investigated retrospectively to study the disease spectrum, associations with neurosyphilis, and therapeutic implications. Ophthalmologic manifestations of syphilitic posterior uveitis are differentiated into acute and chronic uveitides. The several distinct acute uveitic syndromes are usually florid and are associated with early syphilis, with VDRL-positive syphilitic meningitis, and frequently with human immunodeficiency virus coinfection. The chronic posterior uveitides are often insidious, a manifestation of late syphilis, and associated commonly with subclinical neurosyphilis. All patients with acute cases and 54% of patients with chronic cases in our study received penicillin therapy appropriate for neurosyphilis. The frequent association of syphilitic posterior uveitis with neurosyphilis and the analogous spirochetal sequestration beyond the blood-brain and the blood-ocular barriers suggest that all patients with syphilitic posterior uveitis, irrespective of ocular disease intensity, should undergo evaluation of cerebrospinal fluid and be treated with penicillin regimens appropriate for neurosyphilis.

Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay.

Candida endophthalmitis is a serious infection secondary to hematogenous dissemination or direct inoculation of the organisms following trauma or eye surgery. The diagnosis is based on the characteristic findings in the infected eye and on culture of vitreous samples. Unfortunately, the yield of vitreous cultures is limited. The use of a Candida albicans species-specific polymerase chain reaction (PCR) assay in the diagnosis of Candida endophthalmitis is reported herein. Four patients with suspected fungal endophthalmitis underwent vitrectomy for diagnostic and therapeutic purposes. In 2 of the 4, vitreous cultures were negative. However, characteristic PCR products were generated in all 4 patient specimens, enabling the rapid diagnosis of Candida endophthalmitis in all 4. Clinical response was observed in all cases. These results demonstrate the utility of PCR-mediated detection of C. albicans in vitreous samples.

Posterior uveitis in patients with positive serology for syphilis.

The clinical features and ophthalmologic findings of 20 patients with syphilitic posterior uveitis seen at the Detroit Medical Center from November 1993 through February 1996 were reviewed. The mean age was 58 years; 8 patients were male and 12 were female; and all patients were black. Three of 9 patients tested were HIV positive. Patients were divided into 2 groups: those with acute (8) and those with chronic (12) syphilitic posterior uveitis. Chorioretinitis was the predominant uveitic pattern (15/20). Eighteen patients presented with blurred vision. All patients had reactive serum fluorescent treponemal antibody, absorbed (FTA-ABS); 3 had nonreactive rapid plasma reagin (RPR). Mean RPR titer in the chronic uveitis group and in the acute uveitis group was 1:27.3 and 1:209.8, respectively. Seven patients had abnormal cerebrospinal fluid (CSF); CSF VDRL was reactive in 2 patients. All patients were treated with intravenous penicillin G. Eight of 14 patients seen at follow-up showed improvement of ophthalmologic findings. Syphilis should be considered in the differential diagnosis of posterior uveitis.

Race, iris color, and age-related macular degeneration.

PURPOSE: While most observers agree that age-related macular degeneration (AMD) is much more common in white persons than in persons of black African ancestry, the influence of iris color has been more controversial. We reexamined relationships between race, iris color, and AMD in a series of patients from our retina clinic. METHODS: We evaluated, in masked fashion, stereoscopic photographs of the retinas and irides in 306 sequential patients 60 years of age or older from our retina clinics. Four readers judged whether AMD was present, absent, or questionable in the retinal photographs and labeled iris color as blue, hazel, or brown. Presence or absence of AMD and presence and severity of the various macular lesions were determined by "majority vote" of the readers. We evaluated inter-rater agreement using the kappa statistic. We compared the prevalence of AMD and of specific AMD lesions as a function of race, sex, and iris color by contingency table analysis. RESULTS: The kappa statistic showed good inter-observer agreement, being 0.466 (P < 10(-6)) for definite or questionable AMD and ranging from 0.185 to 0.522 (P = 0.0047 to P < 10(-6)) for most lesions. We found significantly more AMD in white patients than in black patients (X2 = 27.54, P < 10(-4)). There was no significant difference in AMD prevalence by sex. In white patients, AMD was significantly more prevalent in individuals with blue or hazel irides than in those with brown irides (X2 = 15.04, P = .02). CONCLUSIONS: We confirm previous findings of a higher prevalence of AMD in white persons than in black persons. We also agree with those observers who claim that white subjects with light-colored irides have a higher prevalence of AMD than those with dark-colored irides. We suggest that differences in the association between iris pigmentation and AMD in different studies using different research methods may reflect genetic difference in the groups being studied.

Mechanisms of retinal arterial occlusive disease in African American and Caucasian patients.

BACKGROUND AND PURPOSE: The aim of our study was to evaluate the causes of retinal arterial occlusive disease in African American patients and to compare these etiologies with those observed in Caucasian patients with retinal ischemic symptoms. METHODS: We performed a retrospective analysis of a series of consecutive patients evaluated by both the ophthalmology department and the neurology/stroke clinic. Patients had a diagnosis of amaurosis fugax, branch retinal artery occlusion, central retinal artery occlusion, or intra-arterial retinal plaques. RESULTS: Twenty-nine African American patients and 17 Caucasian patients were evaluated. African American patients had a mean age of 61 years (range, 30 to 77 years) and Caucasian patients a mean age of 73 years (range, 56 to 94 years) (P=0.003). There was no statistically significant difference between the 2 groups with respect to visible emboli on funduscopy (P=0.462). After adjusting for age, there was also no difference between the 2 groups with regards to risk factors for arterial occlusive disease such as hypertension, coronary artery disease, hypercholesterolemia, tobacco use, and history of stroke or transient ischemic attacks. Caucasian patients had a 41% incidence (7/17) of high-grade ipsilateral internal carotid artery stenosis, measured by carotid duplex, compared with 3.4% incidence (1/29) in African American patients (P=0.002). CONCLUSIONS: There are racial differences in the causes of retinal arterial occlusion. African American patients have a low prevalence of moderate to severe extracranial carotid stenosis, and a high proportion of African American patients have cryptogenic retinal ischemia. In Caucasian patients there is a stronger association between extracranial carotid artery disease and retinal arterial occlusion.

Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration.

PURPOSE: To test the hypothesis that neovascular age-related macular degeneration is related to oxidative stress involving the macular retinal pigment epithelium. This study investigated, as a function of age, levels of enzymes that defend tissues against oxidative stress in the macular retinal pigment epithelium of human eyes with this disease. METHODS: Surgical specimens of macular choroidal neovascular membranes from eyes with age-related macular degeneration and the macular regions of whole donor eyes with neovascular age-related macular degeneration or without evident ocular disease were studied by quantitative electron microscopic immunocytochemistry with colloidal gold-labeled second antibodies. Relative levels in retinal pigment epithelium cell cytoplasm and lysosomes were determined of five enzymes believed to protect cells from oxidative stress, as well as levels of the retinal pigment epithelium marker cytoplasmic retinaldehyde-binding protein, for comparison with the enzymes. RESULTS: Copper, zinc superoxide dismutase immunoreactivity increased and catalase immunoreactivity decreased with age in cytoplasm and lysosomes from macular retinal pigment epithelium cells of normal eyes and eyes with age-related macular degeneration. Cytoplasmic retinaldehyde-binding protein immunoreactivity showed no significant relationship to age or the presence of neovascular age-related macular degeneration. Glutathione peroxidase immunoreactivity was absent from human retinal pigment epithelium cells. Both heme oxygenase-1 and heme oxygenase-2 had highly significantly greater immunoreactivity in retinal pigment epithelium cell lysosomes than in cytoplasm, differing from the much greater cytoplasmic immunoreactivity of the other proteins studied. This immunoreactivity decreased with age, particularly in the lysosomes of retinal pigment epithelium cells from eyes with neovascular age-related macular degeneration. These decreases were of borderline significance (P = .067 for heme oxygenase-1; P = .12 for heme oxygenase-2) when eyes with age-related macular degeneration were compared with normal eyes by multivariable logistic regression. CONCLUSIONS: The high heme oxygenase-1 and heme oxygenase-2 lysosomal antigen levels in macular retinal pigment epithelium cells of eyes with neovascular age-related macular degeneration suggest that oxidative stress causes a pathologic upregulation of these enzymes. Increased lysosomal disposal may indicate that the reparative functions of these enzymes are accompanied by deleterious effects, necessitating their rapid removal from the cell. The much higher heme oxygenase-1 and heme oxygenase-2 antigen levels in macular retinal pigment epithelium cells from younger individuals suggest that protective mechanisms against oxidation and, hence, presumably to the development of age-related macular degeneration, decrease with age.

Corneal topography in Ehlers-Danlos syndrome.

PURPOSE: To assess the use of corneal topography in conjunction with slitlamp biomicroscopy and retinoscopy to diagnose keratoconus in a large group of patients with Ehlers-Danlos syndrome (EDS). SETTING: Kresge Eye Institute, Wayne State University, Detroit, Michigan, USA. METHODS: Thirty-six patients (72 eyes) with genetically typed EDS had slitlamp biomicroscopy, retinoscopy, and videokeratography with the EyeSys instrument. The presence or absence of slitlamp keratoconus findings was correlated to a presumptive diagnosis based on corneal topography using derived topographic indexes associated with keratoconus. These topographic indexes included central corneal power, (CCP), difference in CCP, inferosuperior asymmetry (I-S) value, and asphericity (Q). Axial and profile difference maps were generated and analyzed for findings suggestive of keratoconus. RESULTS: In 72 eyes, no keratoconus was found using slitlamp biomicroscopy. No eye had an I-S value greater than 1.60 diopters (D), 2 eyes had a CCP greater than 46.50 D, and 2 eyes had a Q value less than -1.00. Eight of 36 pairs of eyes had an intereye CCP greater than 0.92 D. In both eyes of the patient with Q values less than -1.00 the profile difference maps were mildly abnormal. CONCLUSIONS: Slitlamp biomicroscopy of the cornea was unremarkable in all patients. Only 1 patient had Q values and profile difference maps that were mildly suggestive of keratoconus. Even after adding topography to the examination, it appears that keratoconus in a known population of patients with EDS remains rare.

Vitreopapillary traction as a cause of elevated optic nerve head.

PURPOSE: To identify vitreopapillary tractional forces as a possible cause of optic nerve head elevation. METHODS: Case reports. Two patients aged 64 and 84 years underwent detailed ocular examination and B-scan ultrasonography. RESULTS: Both patients had a unilateral elevated optic nerve head with normal color vision, normal pupillary responses, and full kinetic perimetry. Biomicroscopic and B-scan ultrasonographic evaluation confirmed the presence of vitreopapillary traction. CONCLUSIONS: Vitreopapillary traction can cause unilateral optic nerve head elevation. The posterior hyaloid should be evaluated in patients with optic nerve head elevation.

Angle-closure glaucoma as an initial presentation of systemic lupus erythematosus.

PURPOSE: To study a patient with bilateral uveal effusions and secondary glaucoma as an initial manifestation of systemic lupus erythematosus. DESIGN: A case report. METHODS: The patient presented with bilateral uveal effusions and angle-closure glaucoma. A detailed ocular examination with ultrasonography and a comprehensive medical evaluation with laboratory testing were performed. RESULTS: The ocular examination revealed bilateral uveal effusions with angle-closure and elevated intraocular pressures. A systemic evaluation revealed bilateral pleural effusions and laboratory values consistent with systemic lupus erythematosus. After medical and laser therapy failed to lower the intraocular pressure, partial thickness sclerectomies, linear sclerostomies, and choroidal drainage were successful in controlling the glaucoma. CONCLUSIONS: Uveal effusion with secondary glaucoma can be a presenting sign for systemic lupus erythematosus. If antecedent ocular abnormalities are not present, a systemic evaluation is warranted in assessing a patient with uveal effusions and secondary angle-closure glaucoma. Partial-thickness sclerectomies, linear sclerostomies, and choroidal drainage may be effective in lowering intraocular pressure.

Phacoemulsification for cataract following pars plana vitrectomy.

BACKGROUND AND OBJECTIVE: To determine if the technical aspects of phacoemulsification for removal of cataract following pars plana vitrectomy differ from those of phacoemulsification for removal of cataract in nonvitrectomized eyes. PATIENTS AND METHODS: Twenty-two eyes that had undergone prior vitrectomy were identified through a retrospective review of chart notes and operative records of 1039 consecutive cataract extractions performed by one surgeon. RESULTS: Complications of proliferative diabetic retinopathy was the most common indication for prior vitrectomy. The predominant lens change was nuclear sclerosis. Deep anterior chambers with large anterior to posterior excursions of the iris lens diaphragm with simultaneous fluctuation in pupil size occurred during phacoemulsification. The posterior capsule was flaccid and mobile during lens cortex removal. No posterior capsules ruptured. Postoperative visual acuity improved in 91% of the patients. CONCLUSIONS: Prior vitrectomy was associated with diabetes and nuclear sclerotic cataract. Phacoemulsification in this patient population was associated with inadequate pupillary mydriasis, superior conjunctival scarring, intraoperative anterior chamber depth, pupil size, and iris lens excursions that hindered phacoemulsification tip placement. Posterior capsules were excessively flaccid, prone to rapid anterior and posterior excursions, and may have plaques that are resistant to intraoperative removal.

Pars plana cicatrization of sewn-in posterior chamber intraocular lens haptics.

The authors describe the unexpected finding of cicatrization of posterior chamber lens haptics to the pars plana. This was found during removal of a secondary, transscleral sewn-in pseudophakos during a retinal reattachment procedure. Ophthalmic history and intraoperative photography revealed pars plana cicatrization of haptics. Despite removal of trans-scleral prolene fixation sutures and application of gentle traction, the posterior chamber lens haptics remained firmly adherent to pars plana retina. The haptics were amputated to prevent significant chorioretinal damage. The conventional belief that all sewn-in posterior chamber intraocular lenses cause little or no scarring response around the haptics may be unfounded.

Chronic Propionibacterium acnes endophthalmitis as a cause of intermediate uveitis.

Although the pathogenesis in most cases of intermediate uveitis is unknown, a small minority of cases is associated with a variety of specific inflammatory etiologies: sarcoidosis; multiple sclerosis; Lyme disease; syphilis; ocular lymphoma; and as a rare manifestation of Behçet's disease and AIDS. A 61-year-old woman developed pars planitis after cataract surgery. A vitrectomy was performed after ten months when a white capsular plaque and an hypopyon developed. Propionibacterium acnes was isolated. The intermediate uveitis was not controlled until later removal of the intraocular lens and capsular remnants. Chronic propionibacterial endophthalmitis may be a cause of intermediate uveitis.

Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears. METHODS: Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascular digest preparations to evaluate microvascular abnormalities. RESULTS: Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations. CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.

AIDS-associated intraocular lymphoma causing primary retinal vasculitis.

BACKGROUND: There is an increasing association between ocular-central nervous system (CNS) lymphoma and the acquired immunodeficiency syndrome (AIDS). In this population, the disease generally occurs in a younger age group. The origin of these B-cell neoplasms remains unknown. METHOD: Case study of a 26-year-old AIDS patient with an incidental finding of localized retinal vasculitis and local vitritis. Disease progression and the failure of antiviral therapy led to early diagnostic vitrectomy with vitreal and retinal biopsy. Cerebrospinal fluid (CSF) evaluation, head magnetic resonance imaging (MRI), and brain biopsy were performed. RESULTS: The diagnosis of ocular non-Hodgkin lymphoma was made by vitreous cytology. Serial sectioning of a retinal biopsy showed no retinal neoplastic infiltration, only perivascular inflammatory cells. CSF was normal. MRI showed multicentric brain mass lesions that enhanced with intravenous contrast. Brain biopsy revealed an immunoblastic, angiocentric, B-cell non-Hodgkin lymphoma. The patient died within two months, despite cerebral and ocular irradiation. CONCLUSIONS: The segmentally localized retinal vasculitis-vitritis and absence of retinal infiltration suggested early primary involvement of the vitreous. Coarse perivascular sheathing is characteristic of the mixed retinal vasculitis in this disease. The diagnosis of ocular-CNS lymphoma must be considered in patients with AIDS, however young, with unexplained posterior segment inflammatory disease or subretinal masses.

Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes.

PURPOSE: To determine whether vascular endothelial growth factor and basic fibroblast growth factor, which may be critical mitogens for neovascularization, are present together in human retinal and choroidal neovascular membranes. METHODS: Light microscopic immunocytochemistry using antibodies against vascular endothelial growth factor, basic fibroblast growth factor, and several cellular "marker" proteins on frozen sections from three choroidal neovascular membranes from patients with age-related macular degeneration, seven surgically excised epiretinal membranes from patients with proliferative diabetic retinopathy, and six epiretinal membranes from patients with nonischemic proliferative retinopathies. RESULTS: All three choroidal neovascular membranes and all seven epiretinal membranes stained positive for vascular endothelial growth factor. Two choroidal neovascular membranes and six of the epiretinal membranes were positive for basic fibroblast growth factor. The same cells were often positive for both antigens. None of the epiretinal membranes from patients with nonischemic proliferative retinopathies were positive for either growth factor. Many of the cells that demonstrated growth factors were glial cells, vascular endothelial cells, and retinal pigment epithelial cells. CONCLUSIONS: Colocalization of two growth factors in the same cells of ocular neovascular membranes suggests that more than one growth factor may contribute to pathologic angiogenesis. Growth factors in neovascular tissues are not localized exclusively in the vascular endothelium. Because expression of some growth factors is stimulated by hypoxia, their localization within choroidal neovascular membranes suggests that hypoxia may be an etiologic factor for choroidal as well as for retinal neovascularization.

Retinal and pregnancy outcomes in the presence of diabetic proliferative retinopathy.

The objective of this study was to examine the retinal and pregnancy outcomes of pregnancies complicated by advanced diabetic retinopathy. Twenty pregnancies complicated by advanced diabetic retinopathy were included in this retrospective study. The data were analyzed to determine trends in perinatal outcome and to document the ophthalmologic performance. Ophthalmologic management included frequent funduscopic examinations by ophthalmologists of the Yale Retina Center. Among the 20 pregnancies, spontaneous abortion occurred in 2 (10%) and stillbirth in 1 (5%); the remaining 17 (85%) pregnancies culminated in live births at a mean gestational age of 36 weeks (+/- 2.3 SD), with a mean birth weight of 2,620 g (+/- 834 SD). The perinatal survival rate was 94%. Photocoagulation therapy was necessary prior to pregnancy in 45%, during pregnancy in 60% and postpartum in 65%. No pregnancies were terminated because of progressive visual changes that did not respond to photocoagulation therapy. Retinal status should not preclude pregnancy since contemporary methods of management can result in satisfactory retinal and pregnancy outcomes even in the presence of advanced diabetic microvascular disease.

Growth factor localization in choroidal neovascular membranes of age-related macular degeneration.

PURPOSE: Because several polypeptide growth factors are known to influence capillary endothelial cell mitogenesis, the authors investigated the presence of some of these molecules in choroidal neovascular membranes (CNVMs) removed surgically from human subjects with age-related macular degeneration (ARMD). METHODS: The authors performed immunoelectron microscopic studies on surgically removed submacular CNVMs from nine subjects with ARMD and from one subject with ARMD whose eye was studied after death. These were compared with retinal pigment epithelial (RPE) and choroidal tissue from eight normal subjects whose eyes were received after death and one received after massive trauma. RESULTS: RPE cells from the CNVMs were strongly immunoreactive for acidic and basic fibroblast growth factor (aFGF and bFGF) and for transforming growth factor beta (TGF beta). Some of the immunoreactivity was intracytoplasmic, but most was intralysosomal. In addition, some choriocapillary endothelial cells located close to the RPE layer in these CNVMs were immunopositive for bFGF and for FGF receptor. Reaction product for these two substances was located at regular intervals along the endothelial plasma membrane on both the anteluminal and the luminal side of the cells, suggesting a physiological reaction between the growth factor and its receptor. Choriocapillary endothelial cells deeper within the stroma were unreactive to bFGF and FGF receptor antibodies. There was little immunoreactivity for the growth factors in RPE or choriocapillary endothelial cells from normal eyes. The aFGF and bFGF immunoreactivity was highly specific because aFGF positivity was abolished when the antibody was incubated with 10(-6) M aFGF but not a with the same concentration of bFGF, whereas bFGF immunoreactivity was abolished by incubation of the antibody with bFGF but not with aFGF. RPE cells from normal eyes and from eyes affected by ARMD showed strong cytoplasmic immunoreactivity to antibodies for cytoplasmic retinaldehyde-binding protein and superoxide dismutase and weak reactivity to antibodies for vimentin. CONCLUSIONS: These results are consistent with the hypothesis that one or both FGFs are causally related to the development of choroidal neovascularization. The authors have reported similar observations in experimental choroidal neovascularization in pigmented rats after red krypton laser photocoagulation. TGF beta may serve to modulate the effects of these mitogens. The authors suggest that growth factor production is induced in RPE cells after physical or chemical damage. Because of the damage to these cells, FGF molecules can be released from the cells despite the absence of a "signal sequence" in the DNA coding for FGF production.