Uncertain compassion in using a drug before the risks and benefits are known.
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Clinical Trials, Phase III as Topic↗
Biomedical subjects
Raja Narayanan
Publications and source records attributed to Raja Narayanan.
Idiopathic macular hole surgery with low-concentration infracyanine green-assisted peeling of the internal limiting membrane.
PURPOSE: To evaluate the efficacy of pars plana vitrectomy with infracyanine green (IFCG)-assisted internal limiting membrane peeling for the treatment of idiopathic macular hole. DESIGN: Prospective, noncomparative interventional case series. METHODS: Thirty-eight consecutive eyes of 35 patients with idiopathic macular hole were included in the study. Patients underwent early treatment diabetic retinopathy (ETDRS) visual acuity examination, dilated ophthalmoscopy, and optical coherence tomography before treatment and during follow-up. Fluorescein angiography was done in selected cases. Patients underwent a three-port pars plana vitrectomy with complete posterior hyaloid and epiretinal membrane removal. The internal limiting membrane (ILM) was stained with 0.5 cc of IFCG (0.5 mg/ml, 308 mOsm) and peeled up to the vascular arcades. Perfluoropropane gas (C(3)F(8)) 10% was used as tamponade. RESULTS: Mean follow-up duration was 10 +/- 5 months (range, 3 to 24 months). Six eyes had stage 2 macular hole, 15 eyes stage 3, and 16 eyes stage 4. Overall, 37 of 38 macular holes closed after a single surgery. Median visual acuity was 20/100 (range, 20/400 to 20/50) before surgery and 20/50 (range, 20/640 to 20/25) after surgery. Visual acuity after surgery was 20/50 or better in 24 of 38 (63.1%) eyes. Twenty-five (65.8%) eyes improved by 2 or more lines, nine (23.7%) eyes were stable, and four (10.5%) eyes worsened by 2 or more lines. CONCLUSIONS: This study suggests that IFCG (0.05%) effectively stains the ILM with apparent safety, and that IFCG-assisted peeling of the ILM may be useful in the treatment of idiopathic macular hole.
Aged↗
Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.
PURPOSE: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001. METHODS: Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities' surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan-Meier analyses and Cox proportional hazards regression models. MAIN OUTCOME MEASURES: Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures. RESULTS: The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0-7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications. CONCLUSIONS: Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.
AIDS-Related Opportunistic Infections↗
Pseudophakic corneal edema: A review of mechanisms and treatments.
PURPOSE: To review the pathological mechanisms and treatments for pseudophakic corneal edema (PCE), one of the most common indications for penetrating keratoplasty. METHODS: The literature was examined for the molecular biology associated with PCE and for the surgical and medical treatments for this disorder. RESULTS: The incidence of PCE has recently been decreasing because of improved surgical instrumentation, including improvements in intraocular lens designs that cause less trauma to the corneal endothelium. Extracellular matrix and growth factor abnormalities occur in PCE corneas and recently, the role of aquaporins, which are involved in the regulation of fluid movement across cells, has been investigated. CONCLUSIONS: Although newer treatment options have been suggested, penetrating keratoplasty still remains the most definitive treatment and has the highest success rate.
Cataract Extraction↗
Toxicity of triamcinolone acetonide on retinal neurosensory and pigment epithelial cells.
PURPOSE: To study the toxicity of triamcinolone acetonide (Kenalog; Bristol-Meyers Squibb, Princeton, NJ) on retinal pigment epithelial (ARPE-19) and retinal neurosensory (R28) cells. METHODS: ARPE-19 and R28 were grown in tissue culture in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum. Cells were treated with 50, 100, and 200 microg/mL concentration of triamcinolone acetonide for 2, 6, and 24 hours. The cells were also treated with the steroid without the vehicle and with the vehicle alone, in which triamcinolone acetonide was suspended. Toxicity was determined by trypan blue dye-exclusion and WST-1 mitochondrial dehydrogenase assays. RESULTS: Vehicle alone did not reduce the viability of ARPE-19 or R28 cells and also did not affect the mitochondrial dehydrogenase activity of the cells. The mean cell viability of ARPE-19 and R28 cells after exposure to triamcinolone acetonide with vehicle 200 microg/mL for 24 hours was 70.7% +/- 10.61% and 75.35% +/- 12.42%, respectively compared with the untreated ARPE-19 (92.7% +/- 6.24%, P < 0.01) and R28 cells (90.63% +/- 5.62%, P < 0.001). The mean cell viability of ARPE-19 cells after exposure to triamcinolone acetonide (200 microg/mL) alone without the vehicle was 84.96% +/- 0.32%, 85.2% +/- 3.26%, and 84.73% +/- 2.71% at 2, 6, and 24 hours, respectively, compared with the untreated ARPE-19 cells (P < 0.001). The R28 cells exposed to triamcinolone acetonide (200 microg/mL) without the vehicle also had a significant reduction in the mean cell viability at 24 hours (86.42% +/- 3.87%, P < 0.001) and 6 hours (89.03% +/- 1.01%, P < 0.01). There was a significant reduction in the mitochondrial dehydrogenase activity in the ARPE-19 cells when treated with both triamcinolone acetonide, with or without the vehicle at a concentration of 200 microg/mL at all time points (P < 0.01). R28 cells did not have any significant reduction in mitochondrial dehydrogenase activity when treated with triamcinolone acetonide without the vehicle at any of the doses, but there was a significant reduction when the R28 cells were treated with triamcinolone acetonide with vehicle (200 microg/mL) for 24 hours (P < 0.05). Triamcinolone acetonide with vehicle caused a greater reduction in cell viability and mitochondrial dehydrogenase activity than did triamcinolone without vehicle, in both cell lines, although the difference was not statistically significant. CONCLUSIONS: Triamcinolone acetonide is toxic to proliferating cells of retinal origin in vitro at doses normally used in clinical practice. The vehicle by itself appears to be nontoxic to the cells, but may have a potentiating effect on the cytotoxicity of triamcinolone acetonide. The results of this in vitro study cannot be directly extrapolated to clinical practice, but, based on these data, further studies may be warranted.
Cell Culture Techniques↗
Activation of caspase-8 and caspase-12 pathways by 7-ketocholesterol in human retinal pigment epithelial cells.
PURPOSE: To determine whether caspase or cathepsin pathways are activated in human retinal pigment epithelial cells (ARPE-19) after exposure to 7-ketocholesterol (7kCh). METHODS: ARPE-19 cells were exposed to 7kCh with or without z-VAD-fmk, a pan-caspase inhibitor. Caspase-3, -8, and -9 activities were measured by a fluorochrome inhibitor of caspase (FLICA) assay. Caspase-12 activity was detected by Western blotting. RT-PCR was performed for 18s, mortalin-2, cathepsins B, D, and L/V2. RESULTS: At 24 hours, 7kCh-treated cultures had increased caspase-8 (P < 0.001) and caspase-3 (P < 0.001) activities compared with vehicle-treated cultures. 7kCh-induced caspase-3 activation was blocked by z-VAD-fmk (P < 0.001). Caspase-9 was not activated by 7kCh treatment (P > 0.05). Procaspase-12 was cleaved into its active form after treatment with 7kCh for 24 hours. At 6 hours, the RNA level for mortalin-2, a pro-survival gene, was upregulated. ARPE-19 cells did not express RNA for cathepsins B, D, or L/V2 under any conditions. CONCLUSIONS: In ARPE-19 cells, 7kCh-induced apoptosis uses the receptor-mediated caspase-8 pathway and the endoplasmic reticulum stress-induced caspase-12 pathway but not the mitochondrial caspase-9 pathway. The cathepsin pathways are not involved in 7kCh-induced cell death. These data demonstrate that 7kCh causes a loss of cell viability through caspase-dependent apoptosis and can act as an oxidative stressor leading to retinal pigment epithelial cell atrophy. Elucidating the specific apoptotic pathways involved may have therapeutic potential for AMD and other retinal diseases.
Amino Acid Chloromethyl Ketones↗
Toxicity of indocyanine green (ICG) in combination with light on retinal pigment epithelial cells and neurosensory retinal cells.
PURPOSE: To evaluate the toxicity of indocyanine green (ICG) in combination with light. METHODS: Human retinal pigment epithelial cells (ARPE-19) and rat neurosensory retinal cells (R28) were treated with four different concentrations of ICG in combination with light exposure. Cell viability, mitochondrial function, and DNA synthesis were measured. RESULTS: All concentrations of ICG with 10 min of light exposure caused a significant decrease in mitochondrial dehydrogenase activity in R28 and ARPE-19 cells. ICG without light exposure did not decrease mitochondrial dehydrogenase activity. In both cell lines, [(3)H]thymidine incorporation was increased when treated with ICG with or without light. R28 cells did not show any significant decrease in cell viability. CONCLUSIONS: The duration of light was a significant factor in ICG toxicity. ICG needs to be used with caution as it decreases the mitochondrial dehydrogenase activity and increases the DNA synthesis in retinal cells, markers for cell toxicity and dysfunction.
Animals↗
Trypan blue: effect on retinal pigment epithelial and neurosensory retinal cells.
PURPOSE: To evaluate the toxicity of trypan blue on retinal cells in vitro. METHODS: Human retinal pigment epithelial cells (ARPE-19) and rat neurosensory retinal cells (R28) were grown in tissue culture and treated with four different concentrations of trypan blue (0.1%, 0.05%, 0.025%, and 0.0125%), in combination with surgical light exposure (0, 5, or 10 minutes). Cell viability, mitochondrial function, and DNA synthesis were measured by trypan blue dye-exclusion assay, mitochondrial dehydrogenase assay, and tritiated [3H] thymidine incorporation, respectively. RESULTS: ARPE-19 and R28 cells exposed to trypan blue with or without illumination did not show any significant decrease, either in cell viability by the dye-exclusion assay or in [3H] thymidine incorporation. R28 cells exposed to 0.1% trypan blue with and without light showed a significant reduction of mitochondrial dehydrogenase activity (P <0.05). ARPE-19 cells exposed to trypan blue, with or without light, did not show any significant decrease in mitochondrial dehydrogenase activity. CONCLUSIONS: This study suggests that rat neurosensory retina (R28) cells are more sensitive than human RPE (ARPE-19) cells to trypan blue. ARPE-19 cells showed no evidence of toxicity with any of the three assays, but R28 cells showed evidence of toxicity with the mitochondrial dehydrogenase assay at the higher doses and light-exposure times studied. Clinical studies must be conducted to determine the safety and efficacy of staining of the inner limiting membrane with trypan blue.
Animals↗
Efficacy of continuous wear PureVision contact lenses for therapeutic use.
PURPOSE: To evaluate the Bausch and Lomb PureVision contact lens as continuous wear contact lens for therapeutic and medical indications in a prospective open-ended non-randomized trial. METHODS: Patients who required therapeutic contact lens wear for various indications such as pain relief, corneal protection, persistent epithelial defects, corneal perforation and chemical burns were fitted with PureVision continuous wear contact lenses (balafilcon A, 36% water content). Success or failure of specific treatment indication was assessed in each case with evaluation of ocular and lens related complications. RESULTS: 30 eyes of 28 patients were fitted with PureVision continuous wear contact lenses. A successful fit was seen in 27 of 30 eyes with therapeutic success in 26 of 30 eyes. However, all patients reported symptomatic relief. Duration of lens use ranged from 3 days to 3 months. Dry eye was the most frequent cause of contact lens associated therapeutic failure. Complications included lens loss (two eyes), tight lens (one eye) and infective keratitis (two eyes). CONCLUSIONS: PureVision contact lenses were found to be safe and efficacious for continuous wear therapeutic use to a maximum of 90 days. The contact lens was also easier to handle by virtue of its resilient nature. There were no significant corneal complications of hypoxia, i.e. corneal oedema. Lens losses and deposits were minimal. The lens performance and fitting characteristics compares favorably with previous therapeutic lenses used by the investigators. This new lens may be considered as a safe and effective alternative for use as bandage contact lens.
Journal Article↗
Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosensory retinal, and microvascular endothelial cells.
PURPOSE: To evaluate the short-term in vitro safety of bevacizumab (Avastin) in human retinal pigment epithelial (ARPE-19), rat neurosensory retinal (R28), and human microvascular endothelial (HMVECad) cells. METHODS: ARPE-19 and R28 cells were treated with 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of bevacizumab for 2, 6, and 24 hours. HMVECad cells were treated with 5 ng/mL of vascular endothelial growth factor (VEGF) and 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of either bevacizumab for 2, 6, and 24 hours or a nonspecific human purified immunoglobulin (IgG) for 24 hours. Cell viability was measured using trypan blue dye exclusion assay. RESULTS: The cell viabilities of ARPE-19 cells, R28 cells, and HMVECad cells treated with bevacizumab were not significantly different (P > 0.05) from that of untreated controls. There was no significant difference (P > 0.05) between viabilities of HMVECad cells treated with bevacizumab and IgG. CONCLUSION: This study suggests that bevacizumab, at concentrations at or above the dose normally used in clinical practice, is not toxic to human retinal pigment epithelial, rat neurosensory retinal, or human microvascular endothelial cells in vitro. This report is consistent with the recent report of lack of toxicity of intravitreal bevacizumab in rabbits as well as the lack of apparent toxicity in clinical use.
Angiogenesis Inhibitors↗
An unusual case of neurofibromatosis fulfilling the diagnostic criteria for types I and II.
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Adolescent↗