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Biomedical subjects

Ivan R Schwab

Publications and source records attributed to Ivan R Schwab.

At least 19 recordsLinked to original sources

Trends of penetrating keratoplasty in the United States from 1980 to 2004.

PURPOSE: To examine the changing trends in penetrating keratoplasties (PKs) performed in the United States. DESIGN: Retrospective review. METHODS: Review of Eye Bank Association of America (EBAA) data on corneal tissue distribution in the United States from 1980 to 2004. Data analysis was retrospective. United States population census data were obtained and used for population-adjusted calculations. A series of Poisson regression models were calculated looking at the temporal trends over time. MAIN OUTCOME MEASURES: The estimated yearly percent change and P values were calculated using Poisson regression models. RESULTS: The total number of corneas distributed for PKs from EBAA member eye banks have steadily increased since 1980. In 1990, the international and domestic distribution data were separated. The total number of PKs performed from EBAA-supplied tissue has continued to rise since 1990; however, the total number of PKs performed in the United States has steadily declined and when population-adjusted rates are examined, the rate of decline is more dramatic. CONCLUSION: Although both absolute numbers and age-adjusted numbers of PKs have declined recently, the population-adjusted rates have dropped more significantly.

Corneal Diseases↗

Inherent risks associated with manufacture of bioengineered ocular surface tissue.

OBJECTIVE: To review the potential health risks associated with bioengineered ocular surface tissue, which serves as a bellwether for other tissues. METHODS: All clinical trials using bioengineered ocular surface tissue published between July 1, 1996, and June 30, 2005, were reviewed with respect to materials used and statements of risk assessment, risk remediation, adverse events, manufacturing standards, and regulatory oversight. RESULTS: Ninety-five percent of investigational protocols used 1 or more animal-derived products and an overlapping 95% used 1 or more donor human tissues. Consideration of risks reveals a very low probability of potential harm but a significant risk of disability or death if such an event were to occur. Details of ethics approval, patient consent, and donor serologic test results were not consistently provided. No references were made to risk assessment or to codes of manufacturing and clinical practice. CONCLUSION: While a degree of risk is associated with bioengineered ocular surface tissue, investigational reports of this new technology have yet to address issues of risk management and regulatory oversight. CLINICAL RELEVANCE: Attention to risk and codes of manufacturing and clinical practice will be required for advancement of the technology. We suggest the adoption of international standards to address these issues.

Cell Culture Techniques↗

UVB irradiation-induced changes in the 27-kd heat shock protein (HSP27) in human corneal epithelial cells.

PURPOSE: This study investigated the presence of the 27-kd heat shock protein (HSP27) and its responses to ultraviolet B (UVB) irradiation in human corneal epithelium and in cultured corneal epithelial cells. METHODS: Human corneal epithelial cells including presumed corneal epithelial stem cells were cultured in vitro. HSP27 expression and intracellular localization in normal corneas or cultured corneal cells were examined using immunofluorescence staining. The expression of HSP27 in cultured corneal cells was also detected using western blotting, and the phosphorylated isoforms of HSP27 were identified using isoelectric focusing. RESULTS: In normal corneal tissue, HSP27 was present in limbal basal and suprabasilar epithelial cells. In cultured epithelial corneal cells, HSP27 expression was heterogeneous: Some cells expressed virtually no HSP27 and others showed relatively strong expression. HSP27 was localized to the cytoplasm in nonstressed cells and translocated to the perinuclear and nuclear areas after UVB irradiation. UVB irradiation also induced the phosphorylation of HSP27, resulting in the increase in monophosphorylated isoform and formation of biphosphorylated isoform. UV induced the phosphorylation of HSP27 apparently through activation of p38 mitogen-activated protein kinase. CONCLUSION: HSP27 is present mainly as a nonphosphorylated isoform in corneal epithelium and cultured corneal epithelial cells under nonstressed conditions. The constitutional expression of HSP27 suggests that it plays a physiologic role in the cornea. After UVB irradiation, HSP27 undergoes rapid phosphorylation and translocation. This stress response may be related to a protective role of HSP27 for survival of UVB-exposed corneal cells.

Blotting, Western↗

Ocular complications of hypovitaminosis a after bariatric surgery.

PURPOSE: To report the ocular complications of xerophthalmia, nyctalopia, and visual deterioration to legal blindness as a result of inadequate vitamin A supplementation after malabsorptive bariatric surgery. DESIGN: Observational case report and literature review. PARTICIPANT: A 39-year-old woman with xerophthalmia and nyctalopia occurring 3 years after gastric bypass surgery. RESULTS: We report a patient with a rare finding of xerophthalmia and visual deterioration after gastric bypass surgery as a result of vitamin A deficiency. The patient was referred for decreased vision associated with chronic dry eyes, bilateral diffuse punctate keratitis, and corneal scarring of unknown cause after several ophthalmologic examinations. The medical history, ophthalmic findings, and clinical course are discussed. CONCLUSIONS: Gastric bypass procedures can cause vitamin A deficiency leading to serious ocular complications, including xerophthalmia, nyctalopia, and ultimate blindness. The increasing incidence of obesity and gastric bypass procedures warrants patient and physician education regarding strict adherence to vitamin supplementation. Education is imperative to avoid detrimental ophthalmic complications resulting from hypovitaminosis A and to prevent a potential epidemic of iatrogenic xerophthalmia and blindness.

Adult↗

Factors modulating p63 expression in cultured limbal epithelial cells.

PURPOSE: The expression pattern of p63, a homologue of the transcription factor p53, and whether it can be used as a corneal epithelial stem cell specific marker remain controversial. We investigated the p63 expression pattern in cultured limbal epithelial cells at different time points in culture, in sparse and confluent cultures, after growth factor starvation, and in single-cell-derived colonies. METHODS: Harvested limbal epithelial cells were plated at 2.5 (sparse) or 5 (dense) x 10 cells/cm and evaluated for p63 expression at day 1, day 4, day 7, after starvation for 72 hours, or in colonies derived from single cells. Expression of corneal lineage specific differentiation marker keratin 3 (K3) was correlated with p63 expression. Results were compared by 1-way ANOVA. RESULTS: More than 85% (85%-90%) of cells expressed p63 on day 1 regardless of cell plating density. On day 4, sparsely plated cultures were subconfluent and demonstrated high p63 expression (87.4%), whereas densely plated cells were confluent and had markedly reduced p63 expression (16.9%). Starvation of subconfluent cultures arrested cell division but did not decrease p63 expression. High-p63-expressing cultures expressed low levels of K3, and this trend was reversed in confluent cultures. Most cells in all colonies derived from single cells expressed p63. CONCLUSIONS: The majority of corneal limbal epithelial cells express p63 in colonies derived from single cells and in subconfluent cultures regardless of time in culture or continuance of cell division. This suggests that p63 expression in culture cannot be used as a marker for stem cells. Significantly reduced number of cells express p63 in confluent cultures, associated with increased cell-cell contact. It is notable that these cells continue to express p63 amid areas of increased cell-cell contact several days after cultures have attained full confluency. This may represent a unique subpopulation of cells that retain proliferative potential in a confluent culture and may be analogous to a subpopulation of stem cells present in vivo.

Adult↗

Dendritic keratopathy in ocular rosacea.

PURPOSE: To report a case of dendritic keratopathy secondary to ocular rosacea in a 62-year-old man. METHOD: Case report. RESULTS: We discuss the ophthalmologic findings, management, and course in a patient with an unusual dendritic corneal lesion resistant to medical therapy. Other causes of dendritic lesions on the cornea were ruled out after investigation. The patient experienced symptomatic and objective improvement in the lesion with treatment of ocular rosacea. CONCLUSION: This case represents an interesting presentation of rosacea with dendritic keratopathy associated with typical skin lesions.

Androstadienes↗

The long-term results of keratoplasty in eyes with a glaucoma drainage device.

PURPOSE: To study the outcome of penetrating keratoplasty (PK) in eyes with a glaucoma drainage device (GDD). DESIGN: Retrospective case-controlled study. METHODS: We reviewed all patients who underwent PK from December 1986 to September 2002 at the University of California, Davis (n = 1,974). We identified 33 patients (40 grafts) who were treated with a GDD and followed up for 6 months or more after PK. Graft survival and glaucoma control were compared with grafts in patients without glaucoma (n = 40) and patients with medically controlled glaucoma (n = 17). Kaplan-Meier survival analysis, log rank test, repeated-measures analysis of variance (ANOVA), Fisher exact test, and chi(2) were used in group comparisons. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: The percentages of clear grafts in the glaucoma drainage device group were 58.5% and 25.8% at 1 and 2 years, respectively. At these time points, glaucoma was controlled in 74.0% and 63.1% of the eyes, respectively. Both medically controlled glaucoma patients and nonglaucomatous patients had higher graft survival percentages at comparable time points. The presence of a GDD was an important factor influencing graft survival (Hazard ratio = 6.8). CONCLUSION: A GDD implant is an independent risk factor for graft failure. Although these devices are effective in controlling intraocular pressure (IOP) in the majority of eyes in the presence of PK, corneal graft clarity is often compromised.

Adolescent↗

Central retinal vein occlusion and renal cell carcinoma.

PURPOSE: To document a case of central retinal vein occlusion (CRVO) associated with renal cell carcinoma and elevated levels of anticardiolipin and antiphospholipid antibodies. DESIGN: Observational case report. METHODS: History, clinical examination, chart review, and laboratory serologies were performed on a 63-year-old man with renal cell carcinoma with a 6-week history of decreased vision in his left eye. RESULTS: Vision was 20/40 in the left eye. Dilated fundus examination revealed a CRVO. Laboratory serologies revealed markedly elevated levels of anticardiolipin and antiphospholipid antibodies. CONCLUSION: This case illustrates an association between CRVO and renal cell carcinoma. A paraneoplastic process, consisting of both antiphospholipid and anticardiolipin antibodies, may be a mechanism for CRVO.

Antibodies, Anticardiolipin↗

A phase III clinical trial of 0.5% levofloxacin ophthalmic solution versus 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis.

OBJECTIVE: To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (QUIXIN) with 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis. DESIGN: Prospective, randomized, active-controlled, double-masked, multicenter study. PARTICIPANTS: Four hundred twenty-three patients with a clinical diagnosis of bacterial conjunctivitis were enrolled. METHODS: Patients were randomly assigned to receive either 0.5% levofloxacin (n = 211) or 0.3% ofloxacin (n = 212) for 5 days (every 2 hours on days 1 and 2 and every 4 hours on days 3-5). Conjunctival cultures were obtained, and ocular signs and symptoms were evaluated on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). End point was defined as the last evaluable observation. MAIN OUTCOME MEASURES: Primary microbial and clinical outcomes were based on culture results and resolution of cardinal signs, respectively. Secondary efficacy assessments included evaluations of ocular signs and symptoms. RESULTS: Two hundred eight patients (levofloxacin, n = 109; ofloxacin, n = 99) were evaluated for efficacy. Microbial eradication rates were significantly greater in the 0.5% levofloxacin treatment group compared with the 0.3% ofloxacin group at both the final visit (89% vs. 80%, P = 0.034) and at end point (90% vs. 81%; P = 0.038). Treatment with 0.5% levofloxacin was significantly more effective in resolving photophobia than was 0.3% ofloxacin treatment (94% vs. 73%, P = 0.006). Both study medications were well tolerated, with a low incidence of adverse events. CONCLUSIONS: Although clinical cure rates in the 0.5% levofloxacin and 0.3% ofloxacin treatment groups were similar, a 5-day treatment regimen with 0.5% levofloxacin achieved microbial eradication rates that were statistically superior to those attained with 0.3% ofloxacin. Despite the higher concentration of active drug in 0.5% levofloxacin versus 0.3% ofloxacin, there was no difference between treatment groups in the incidence of treatment-related adverse events.

Adolescent↗

Multifocal choroiditis in patients with familial juvenile systemic granulomatosis.

PURPOSE: To document clinical features of uveitis in patients with familial juvenile systemic granulomatosis. DESIGN: Retrospective chart review. METHODS: Ophthalmologic examination, medical history, and clinical course in 16 patients from eight families examined at six academic medical centers. RESULTS: Of the 16 patients, 15 had evidence of panuveitis with multifocal choroiditis. One patient had only an anterior uveitis. Ischemic optic neuropathy, presumably due to a small vessel vasculopathy, and retinal vasculopathy each occurred in one patient. Ocular complications were common, including cataracts in 11, glaucoma in six, band keratopathy in six, cystoid macular edema in six, and optic disk edema in six. All 16 patients had polyarthritis, and at least nine had skin rash. Often patients were misdiagnosed initially as having either juvenile rheumatoid arthritis or sarcoidosis. CONCLUSIONS: Familial juvenile systemic granulomatosis is an uncommon genetic disease characterized by polyarthritis and uveitis. Panuveitis and multifocal choroiditis often may be present. Patients with a diagnosis of juvenile rheumatoid arthritis but having a family history of the disease and multifocal choroiditis should be suspected of having familial juvenile systemic granulomatosis.

Adolescent↗

A fibrin-based bioengineered ocular surface with human corneal epithelial stem cells.

PURPOSE: The purpose of the investigation was to prepare a bioengineered ocular surface tissue replacement consisting of (presumed) human corneal epithelial stem cells in a cross-linked fibrin gel for potential transplant. METHODS: Presumed human epithelial stem cells were harvested, isolated, and cultivated as previously described from adult donor corneas obtained from a tissue and organ bank. The cultured corneal epithelial stem cells were suspended in a fibronectin/fibrin gel cross-linked by factor XIII. Plasma components were derived from a fibrinogen-rich cryoprecipitate of human plasma. Suspended cells proliferated in the fibrin gel, giving rise to colonies that eventually coalesced to near confluence over the 15 days of cultivation. The gels were sectioned and immunostained for keratin 3 (AE5) and keratin 19. RESULTS: The fibrin gel product with corneal stem cells was easily manageable and maneuverable. Addition of the protease inhibitor aprotinin to the incubation medium prevented gel degradation; once it was removed, gels disintegrated within 24 hours. All of the cells cultivated in the fibrin gel stained positively for keratin 3 (AE5), indicating differentiation along the corneal epithelium lineage. Cells located in the center of the colonies were keratin 19-positive, suggesting a more primitive cell type. Growth kinetics were documented. CONCLUSIONS: A bioengineered ocular surface with a combination of presumed corneal epithelial stem cells in a cross-linked fibrin gel represents a potential improvement in current attempts to create a transportable, pliable, and stable tissue replacement. Since both the cells and the plasma components of the fibrin gel are of human origin, this technique provides the potential for a totally autologous bioengineered replacement tissue.

Adult↗

The relationship between first postoperative day epithelial status and eventual health of the ocular surface in penetrating keratoplasty.

PURPOSE: To determine a possible relationship between donor epithelial status on the first postoperative day after keratoplasty and the eventual health of the corneal surface. METHODS: We analyzed 91 patients who underwent penetrating corneal transplantation between January 1998 and January 2000, monitoring the epithelial status of the corneas with fluorescein staining using slit-lamp biomicroscopy. Recipient pre- and postoperative variables and donor characteristics were recorded. Macroepithelial defects were classified into three groups according to the extent of the epithelial defect. The results on the first postoperative day were compared with the first and third operative month. Donor and recipient variables were compared with the epithelial status on the first and third month as well. RESULTS: On the first postoperative day, 64.84% of the patients had epithelial defects, 10.99% had defects at the 1-month postoperative visit, and none had defects at the third month. Graft recipients with macroepithelial defects in the first postoperative month were older, had a higher prevalence of blepharitis, higher prevalence of inadequate eye hydration, and slightly increased corneal sensation compared with the group without epithelial defects; however, none of these trends were statistically significant. Patients with macroepithelial defects in the first postoperative month received older donor tissue, and the average preservation-to-surgery time was longer. These donor variables, however, were not significant statistically (p value >0.10) in determining outcome of the epithelial status at the first or third months. CONCLUSIONS: Our results suggest that the epithelial status on the first postoperative day is not predictive of surface integrity at 1-month postoperative (p value is 0.2676 for the likehood ratio test). The epithelial status on the first postoperative day is not predictive of the status of the third month after keratoplasty, because none of the 91 patients had epithelial defects after 3 months.

Age Factors↗