Diagnostic and therapeutic challenges. High grade fever and bronchitis.
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2-Aminopurine↗
Biomedical subjects
Janet L Davis
Publications and source records attributed to Janet L Davis.
Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display.
Autoimmune uveitis is a group of ocular inflammatory disorders with unknown causes. As in other autoimmune diseases, identification of autoantigens from uveitis patients would markedly improve our understanding of the disease mechanism. Here, we report that a candidate autoantigen was identified by phage display in an unbiased fashion. A bacteriophage T7 display cDNA library was generated from human eye and characterized. Patient-specific phages were enriched by four rounds of phage display with purified patient IgG. Enriched phages demonstrated a 20-fold increase in binding specificity to the patient IgG compared with control IgG. Two clonal phages with particularly high relative binding specificities were isolated and characterized. The encoded genes, tribbles homolog 2 (TRB2) and an unknown protein, had 170- and 42-fold increases in their binding specificities to the patient IgG, respectively. The patient-specific immunoreactivities were further confirmed by Western blotting. Anti-TRB2 antibody activities were detected in several uveitis patients but not in control subjects, suggesting that TRB2 is a uveitis-associated candidate autoantigen. These results demonstrate that autoantigens can be identified by phage display using uveitis patient serum.
Antibody Specificity↗
Outcomes of complex retinal detachment repair using 1000- vs 5000-centistoke silicone oil.
OBJECTIVE: To compare anatomic and visual acuity outcomes, as well as complication rates, after retinal detachment repair using 1000- vs 5000-centistoke silicone oil. METHODS: Records of all patients who underwent retinal detachment repair with silicone oil at one institution between January 1, 1995, and December 31, 2000, were reviewed. Anatomic outcomes included retinal redetachment and macula-off retinal redetachment. Visual acuity outcomes included ambulatory vision (> or =5/200) and change in visual acuity from preoperative examination. Complications included rates of secondary intraocular pressure elevation, hypotony, corneal opacification, cataract, and oil emulsification. Outcomes were assessed at 1 week, 1 month, 3 months, 6 months, and 1 year. RESULTS: The study included 82 eyes that underwent retinal detachment repair with 1000-centistoke silicone oil and 243 eyes that underwent retinal detachment repair with 5000-centistoke silicone oil. Demographic characteristics, cause of retinal detachment, and preoperative ocular characteristics were similar in the 2 groups. There was no significant difference in the rate of retinal redetachment at each of the follow-up intervals investigated. The cumulative retinal detachment rate was also similar between the 2 groups except among trauma cases, for which 1000-centistoke silicone oil was associated with a higher cumulative redetachment rate (P<.001). There was no significant difference between the groups with respect to (1) change in visual acuity from preoperatively to 6 months postoperatively and (2) the proportion of patients who achieved ambulatory vision at each of the follow-up intervals investigated. Rates of elevated intraocular pressure, hypotony, corneal abnormality, cataract, and silicone oil emulsification were similar in the 2 groups. CONCLUSIONS: Anatomic and visual acuity outcomes, as well as complication rates, were similar in both groups; retinal reattachment and ambulatory vision were achieved in most eyes regardless of oil viscosity.
Adolescent↗
Electroretinographic monitoring in birdshot chorioretinopathy.
PURPOSE: To evaluate electroretinography (ERG) during long-term follow-up in birdshot chorioretinopathy (BCR). DESIGN: Retrospective, comparative interventional case series. METHODS SETTING: University subspecialty clinic. PATIENT POPULATION: Twenty-three HLA-A29-positive patients with BCR and 40 normal control subjects. INTERVENTION PROCEDURE: Patients were monitored with ERG approximately annually. Treatment was according to best medical judgment. main outcome measures: Baseline ERG values, vision, and ERG values during observed and treated intervals. RESULTS: Median age of patients was 52 years, and 19 patients were untreated at baseline. Eighty-two ERGs were performed. Eighteen patients had more than one ERG; mean follow-up of these patients was 40.2 months +/- 31.2, median 23 months. At baseline, several ERG parameters were statistically reduced compared with control subjects when adjusted for age. The combined rod-cone and cone b/a wave ratios did not differ from control subjects (P = .45 and 0.14). Scotopic rod and combined rod-cone b-wave amplitudes were statistically correlated with baseline vision, as were implicit times for the combined rod-cone a-wave, cone a-wave, and cone flicker b-wave. Median visual acuity was 20/25 and did not change during follow-up. Most ERG parameters showed marked worsening during observed intervals. During treated intervals, the ERG declined at a rate consistent with aging. CONCLUSIONS: Many ERG parameters in patients with BCR greatly differ from control subjects, correlate with vision, and worsen during observation. Selected patients may show improvement in ERG with treatment. The cone b-wave flicker implicit time was most often associated with clinically important measures such as vision, duration of symptoms, and deviation from normalcy.
Adult↗
Diagnostic testing of vitrectomy specimens.
PURPOSE: To assess the usefulness of diagnostic tests that are performed on vitrectomy specimens from patients with suspected lymphoma or infection. DESIGN: Noncomparative, retrospective, interventional case series. METHODS: Seventy-eight consecutive patients (84 eyes) underwent pars plana vitrectomy for diagnostic purposes. Vitrectomy with cytologic, cytofluorographic, or microbiologic analysis of vitreous samples was performed. The main outcome measures were the efficiency of diagnostic procedure and positive and negative predictive values (PPV and NPV). RESULTS: There were 28 patients (33 eyes) with suspected intraocular lymphoma and 50 patients (51 eyes) with suspected infection, which was subdivided into chronic endogenous endophthalmitis, atypical chorioretinitis, or chronic postoperative inflammation. Vitreous testing led to a diagnosis in 48 of 78 patients (61.5%); 14 patients with a final diagnosis of lymphoma/leukemia, and 34 patients with a final diagnosis of infection. When preoperative indication was compared with final clinical diagnosis, the efficiency of the diagnostic procedure of cytologic evaluation, flow cytometry, and bacterial/fungal culture was 67%, 79%, and 96%, respectively. For lymphoma, the PPV of cytologic evaluation was 100% and the NPV 60.9%. For infection, the PPV of bacterial/fungal culture was 100% and the NPV 94.9%. CD22+ B lymphocytes >or=20% of total cells on cytofluorographic analysis had a PPV of 88% for lymphoma. A cytofluorographic CD4:CD8 T-lymphocyte ratio >or=4 had a PPV of 70% for immunologically mediated uveitis. Surgical complications were rare and manageable. CONCLUSION: Diagnostic vitrectomy in selected patients with carefully planned testing is an effective means of supporting diagnoses in intraocular lymphoma, chronic intraocular infections, and atypical chorioretinitis. Flow cytometry quantitates the percentages and ratios of various cell types and is helpful in contrasting intraocular lymphoma with immunologically mediated uveitis.
Adult↗
Acute acquired toxoplasma retinitis may present similarly to unilateral acute idiopathic maculopathy.
PURPOSE: To describe a patient with acquired toxoplasma retinitis that shared similarities with unilateral acute idiopathic maculopathy. DESIGN: Interventional case report. METHODS: Interventional case report. RESULTS: A 39-year-old woman presented with sudden unilateral vision loss in the right eye after a flu-like illness. She had retinitis involving the fovea, subretinal fluid, thickening of the retinal pigment epithelium, and a few vitreous cells; the retinitis resolved with antitoxoplasma antibiotic treatment. CONCLUSIONS: Acute acquired toxoplasma retinitis may present similarly to unilateral acute idiopathic maculopathy.
Acute Disease↗
Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes.
PURPOSE: To investigate clinical features and visual acuity outcomes associated with endogenous endophthalmitis. DESIGN: Retrospective, observational case series. METHODS: Twenty-one eyes of 21 patients treated at Bascom Palmer Eye Institute for culture-proven endogenous endophthalmitis between 1996 and 2002 were reviewed. RESULTS: Patients were followed a mean of 3 months (range, 1 to 12 months). Fungal isolates occurred in 13 eyes (62%), gram-positive isolates in 7 (33%), and gram-negative isolates in 1 (5%). Twelve patients (57%) were hospitalized at the time of diagnosis and 6 patients (29%) died within 2 months of diagnosis. Initial treatment included tap and injection of intravitreal medication in 10 eyes (48%) and pars plana vitrectomy with injection of intravitreal medication in 11 eyes (52%). Final visual outcomes were obtainable for 18 eyes (two patients died within 10 days of diagnosis, and one patient was lost to follow-up). Eight (44%) of these 18 eyes achieved a visual acuity of 20/400 or better and 10 (56%) of 18 eyes achieved a visual acuity worse than 20/400, including 3 that were either enucleated or eviscerated. Three eyes with Aspergillus endophthalmitis had worse visual outcomes than eyes with either Candida (P =.036) or bacterial endophthalmitis (P =.024). CONCLUSIONS: Compared with published series of postoperative or post-traumatic endophthalmitis, patients with endogenous endophthalmitis are more likely to have fungal isolates with a predominance of Candida albicans. Endogenous endophthalmitis is generally associated with high mortality and poor visual acuity outcomes, particularly when caused by more virulent species such as Aspergillus.
Adult↗
Diagnostic approaches to severe, atypical toxoplasmosis mimicking acute retinal necrosis.
PURPOSE: To describe the means of diagnosis and clinical features of atypical toxoplasmic chorioretinitis mimicking acute retinal necrosis. DESIGN: Observational case series. PARTICIPANTS: Twenty-two patients (25 eyes) with widespread chorioretinitis resulting from toxoplasmosis examined between 1990 and 2001. TESTING: Patients were diagnosed by various techniques, including polymerase chain reaction (PCR) of aqueous and vitreous, serum and intraocular antibody determination, culture of intraocular fluid, retinal biopsy, histopathologic examination, therapeutic trial of antibiotics active against toxoplasmosis, or a combination thereof. MAIN OUTCOME MEASURES: The primary outcome measure was diagnosis of disseminated toxoplasmic chorioretinitis by any combination of tests or by empiric use of specific antibiotics. The secondary outcome measure was visual and anatomic outcome of treatment. RESULTS: Mean age was 53.5 years (range, 19-77 years), with a median of 59.5 years. There were 9 women and 13 men. Six patients were infected with HIV, and 3 patients, 1 with HIV, had bilateral disease. Mean initial vision was 20/110 (median, 20/400; range, 20/20 to no light perception [NLP]). Sixteen patients (73%) had received oral or injectable corticosteroids and 11 (50%) had received antiviral therapy before the diagnosis of toxoplasmosis. Diagnosis was made solely by clinical response to antitoxoplasmosis medications in 4 patients. Sixteen patients were diagnosed based on evaluation of intraocular fluids and tissue by antibody determinations, culture, PCR, histopathologic examination, or a combination thereof. Visual acuity improved after treatment in 7 of 25 eyes (28%). Mean final visual acuity was 20/156 (median, 20/2500; range, 20/30 to NLP). Anatomically, 18 of 23 eyes with follow-up had healed or improved chorioretinitis. Retinitis was progressive in 1 eye, 2 eyes were enucleated, and 2 were phthisical. CONCLUSIONS: Diagnosis of atypical toxoplasmic chorioretinitis that mimics viral retinitis can be accomplished by several means. Prompt diagnosis may help avoid poor visual and anatomic outcomes after prolonged initial treatment with oral prednisone or antiviral medications.
Adult↗
Ocular complications of pediatric uveitis.
PURPOSE: To determine the cumulative proportion and the visual significance of ocular complications of pediatric uveitis. DESIGN: Cohort study. PARTICIPANTS: Patients with onset of endogenous or infectious uveitis before or at age 16 years. METHODS: Retrospective review of existing records at a university-based uveitis clinic. MAIN OUTCOME MEASURES: Type and prevalence of complications related to uveitis, time to development of complications, and vision loss after initial diagnosis. RESULTS: There were 148 patients, 71 males and 77 females, with a mean age of 10.4+/-4.9 years (median, 10.3 years) for an estimated prevalence of pediatric uveitis of 13.8%. Noninfectious uveitis was present in 112 patients (75.7%); 105 (71%) patients had bilateral disease. Anterior uveitis accounted for 30.4%, intermediate uveitis for 27.7%, posterior uveitis for 23.7%, and panuveitis for 18.2% of patients. Patients were followed for a mean of 71.7 months (range, 0 months-44 years) after diagnosis. Approximately 34% of all patients had 1 or more complications at the time of first diagnosis of uveitis by an ophthalmologist, increasing to 61.6% by 3 months, 69.4% by 6 months, 75.2% by 1 year, and 86.3% by 3 years after diagnosis. There were a total of 617 complications of all types. Anterior and intermediate uveitis had a higher risk of band keratopathy (P = 0.005). Posterior and intermediate uveitis had a lower risk of cataract (P = 0.009) or posterior synechiae (P<0.001). Intermediate uveitis had a higher risk of cystoid macular edema compared with anterior or posterior uveitis (P = 0.002). The cumulative percentages (standard error) of patients with first loss to 20/200 or worse after diagnosis in the affected eyes of unilateral cases or in either eye of the bilateral cases were: 31.3% (3.9) at 1 month; 40.5% (4.1) at 6 months; 56.0% (4.3) at 24 months; and 69.6% (4.5) at 60 months. Fifty-four patients (48.2%) received systemic antiinflammatory or immunomodulatory therapy. Sixty-eight patients (45.9%) had ocular surgery, and 38 of these had ocular surgery in both eyes. CONCLUSIONS: Childhood uveitis is significant for numerous complications, many of which are vision threatening. Complications increase with duration of disease.
Adolescent↗
Diagnosis of intraocular lymphoma.
PURPOSE: To review current techniques for the diagnosis of intraocular lymphoma. METHODS: Literature review. RESULTS: There are a limited number of small case series and case reports reporting the diagnosis of intraocular lymphoma. Limitations in the ability to diagnose lymphoma through cytologic examination of the vitreous has led to investigations into immunohistochemistry either manually or by automated cytofluorography, intraocular cytokine determinations, and polymerase chain reaction of the vitreous or tissue lymphoid cells to detect gene rearrangements in the IgH, bcl-2, or T-cell receptor gamma gene. Data regarding diagnostic efficiency of the various testing strategies is limited by small patient numbers. Careful handling of the vitreous specimen and adequate laboratory and pathological support is critical. CONCLUSIONS: Despite a proliferation of new techniques for the diagnosis of intraocular lymphoma, none is clearly superior. Use of multiple testing strategies may improve diagnostic yield.
Diagnostic Techniques, Ophthalmological↗
Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis.
PURPOSE: To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes. DESIGN: Prospective cohort study. METHODS: Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or = 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0 micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes. RESULTS: One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all < or = .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P =.012 to.021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P =.009 to.096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction. CONCLUSIONS: The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.
AIDS-Related Opportunistic Infections↗
Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids.
PURPOSE: To report two cases of progressive outer retinal necrosis occurring in immunocompetent individuals after treatment with corticosteroids for presumed optic neuropathy. DESIGN: Observational case report. SETTING: University-based tertiary eye hospital. METHODS: Retrospective review of existing clinical records. RESULTS: Two patients were treated empirically with systemic corticosteroids for suspected inflammatory papillopathy. Subsequently, both were diagnosed with necrotizing herpetic retinitis with features of progressive outer retinal necrosis. Anterior chamber paracentesis confirmed varicella-zoster infection. Both patients were human immunodeficiency virus negative; one patient with rheumatoid arthritis was taking etanercept. Both became completely blind in one eye despite intensive treatment with antiviral medication intravenously and intravitreally. CONCLUSIONS: Progressive outer retinal necrosis is not confined to patients with underlying severe immunodeficiency, such as acquired immune deficiency syndrome. Initial treatment of acute, unexplained vision loss with systemic corticosteroids may lead to catastrophic visual loss in patients with evolving necrotizing herpetic retinopathy.
Acyclovir↗
Laser flare photometry and complications of chronic uveitis in children.
PURPOSE: To investigate possible relationships between laser flare photometry values, complications of uveitis, and outcomes in children with chronic uveitis. DESIGN: Retrospective chart review. METHOD: We evaluated patients with active, noninfectious anterior, intermediate, or panuveitis who were 16 years of age or younger and who had laser flare photometry at one of two academic institutions. Complications enumerated at baseline and during follow-up were compared with laser flare photometry values and to anterior chamber cell counts. RESULTS: At least one laser flare photometry value ("flare"), defined as baseline measurement, was available for 59 patients (41 girls, 18 boys; mean age, 10.3 +/- 3.5 years); 38 of these patients had at least one additional measurement during follow-up (median 11 months). Complications of uveitis were present in 35 patients (59%) at baseline. There was a positive association between increased laser flare photometry values and complications at baseline (any complication [P =.007], posterior synechiae [P =.003]). The development of complications during follow-up was associated with the presence of complications at baseline (P =.018). A subgroup of patients with low flare at baseline had no complications during follow-up regardless of treatment given. CONCLUSIONS: There is a positive relationship between laser flare photometry values and the prevalence of complications of uveitis in children. Laser flare photometry provides a novel way to monitor children with uveitis. Future study will be needed to determine whether values have prognostic importance and whether a treatment strategy that minimizes flare results in fewer uveitic complications.
Aqueous Humor↗
Optical coherence tomographic findings in acute exudative polymorphous vitelliform maculopathy.
PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy. DESIGN: Observational case reports. METHODS: Fluorescein angiography, optical coherence tomography, and electrophysiology were performed. RESULTS: Both patients presented with sudden onset of blurred vision and bilaterally symmetric, central, and perimacular vitelliform lesions. Perimacular lesions were faintly hyperfluorescent early in the disease, but there was no abnormal fluorescence in the macular centers. Optical coherence tomography revealed anterior displacement of the photoreceptor layer by a hypereflective subretinal layer overlying a hyporeflective space above the retinal pigment epithelium-choriocapillaris complex under all lesions and no subretinal fluid. The electrooculogram was abnormal. Near complete resolution occurred over 4 to 8 months, with no improvement in the electrooculogram. CONCLUSIONS: Transient multifocal vitelliform lesions suggest a diagnosis of acute exudative polymorphous vitelliform maculopathy. Optical coherence tomography reveals characteristic anterior displacement of the photoreceptor layer by a subretinal hypereflective deposit similar to that seen in adult-onset foveomacular vitelliform dystrophy.
Acute Disease↗
Bilateral choroidal effusions associated with dengue fever.
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Aged↗
Comparison of cytomegalovirus (CMV) UL97 gene sequences in the blood and vitreous of patients with acquired immunodeficiency syndrome and CMV retinitis.
Cytomegalovirus (CMV) resistance to ganciclovir occurs via mutations in the UL97 gene. CMV DNA, from vitreous and blood specimens and from culture isolates from 87 patients with acquired immunodeficiency syndrome and CMV retinitis who received a ganciclovir implant, was sequenced to identify the relationship between the UL97 DNA sequences in the eye and peripheral blood. There was 93.5% agreement between the UL97 gene sequences from paired vitreous specimens and blood specimens. Sequence analysis of vitreous specimens showed that 15% (13/87) of the patients had either a ganciclovir resistance-conferring mutation or a polymorphism in the CMV UL97 gene. Eleven of the 13 mutations or polymorphisms in the vitreous also were identified in blood. Although the number of mutations limits definitive interpretation, these data suggest that blood specimens may reflect the events occurring in the eyes of patients with CMV retinitis.
AIDS-Related Opportunistic Infections↗
Clinicopathologic reports, case reports, and small case series: clinicopathologic correlation of idiopathic polypoidal choroidal vasculopathy.
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Choroid↗
Atypical anterior optic neuropathy caused by toxoplasmosis.
PURPOSE: To report atypical anterior optic neuropathy due to toxoplasmosis. METHODS: Interventional case report. A 33-year-old male presented with sudden painless loss of vision and floaters in the right eye. Examination demonstrated a best-corrected visual acuity of 20/200, optic nerve head edema, retinal hemorrhages, and vitreous opacities. RESULTS: Nine days later, a granuloma at the optic nerve head was apparent, and the patient was treated with pyrimethamine, sulfadiazine, folinic acid, and prednisone. Six weeks after initiating therapy, best-corrected visual acuity had improved to 20/25. CONCLUSION: Optic nerve involvement in toxoplasmosis is uncommon and, when it occurs, usually presents with a white inflammatory mass on the optic disk. The current case demonstrates the importance of including toxoplasmosis in the differential diagnosis of unilateral anterior optic neuropathy, even if a focal inflammatory mass is not apparent.
Adult↗