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ABSTRACT: INTRODUCTION: The aim of this study was to comparatively analyze the effects of topical intraocular pressure (IOP)-lowering drugs on the ocular surface and to elucidate whether the main causative factor of toxicity is associated with benzalkonium chloride (BAK) or an active compound. METHODS: The medical records of 300 eyes in 187 glaucoma patients that had instilled IOP-lowering drugs were cross-sectionally reviewed. Corneal epithelial punctuate erosion and tear break-up time (BUT) were quantitatively assessed. Durations of glaucoma, sums of concentrations of BAK in current medication (BAK%sum), and the presence of beta-blockers were investigated as risk factors (Institutional Review Board of Seoul National University Hospital, Seoul - IRB number: H-1007-103-324). RESULTS: Age-adjusted BAK%sum was found to be significantly and positively correlated with corneal epithelial punctate erosion (P = 0.001, r = 0.208) and negatively correlated with BUT (P = 0.042, r = 0.131). BAK%sum adjusted corneal epithelial erosion was found to be significantly greater in beta-blocker containing eyedrop-instilled eyes (P = 0.016). No difference in ocular toxicity was found between carbonic anhydrase inhibitor and prostaglandin analog or between latanoprost- and travoprost-treated eyes. CONCLUSION: Long-term treatment with BAK-containing antiglaucoma medication appears to be the main contributor to corneal toxicity and to do so in a dose-dependent manner. Formulations containing beta-blockers also appear to contribute to corneal toxicity.
Advances in Therapy 04/2013; · 2.11 Impact Factor
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ABSTRACT: To investigate effects of a new push-through insertion method for donor lenticules using an injector system on endothelial viability ex vivo and in a clinical case series of endothelial keratoplasty.
An ex vivo delivery model was used with porcine corneoscleral rims. We compared the endothelial viability in a new push-through insertion method using the Visian Implantable Collamer Lens (ICL) injector versus that of standard forceps-assisted insertion for lenticule delivery. Twenty porcine corneal lenticules were divided into four groups by insertion method and wound size. Vital dye staining was performed and devitalized areas were semi-quantitatively assessed by digital imaging. In the clinical case series, Descemet's stripping endothelial keratoplasty (DSEK) using the push-through method was performed in seven patients and endothelial outcome was determined six months postoperatively.
Mean devitalized areas for the push-through method were significantly lower than for forceps-assisted insertion through 3.2 mm incision (23.99 ± 2.17% vs. 50.48 ± 5.07%, p = 0.009) in the ex vivo model. Average endothelial cell counts of donor tissues of patients who underwent DSEK were 26.4% lower six months postoperatively.
Push-through delivery of donor lenticules using the Visian ICL injector system appears to be less harmful to endothelial cells than conventional forceps-assisted delivery.
Korean Journal of Ophthalmology 04/2013; 27(2):87-92.
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ABSTRACT: PURPOSE:: To evaluate the effects of oral ambroxol on tear film and ocular surface. METHODS:: Twenty healthy male subjects with no ocular disease were recruited. Subjects were divided into 2 groups: a control group and an ambroxol group. Ambroxol hydrochloride was administered orally to the ambroxol group. The tear film and ocular surface were evaluated at baseline (10 AM), 12 PM, 6 PM, and 10 AM the next day. Visual analog pain scale, tear film break-up time, fluorescein corneal staining, Schirmer test, tear osmolality, and fluorescein clearance test were measured. RESULTS:: The mean visual analog pain scale score increased at 6 PM and 10 AM the next day in the ambroxol group (P = 0.007 and P = 0.018, respectively). The tear film break-up time did not show any significant change in the control group and shortened at 6 PM in the ambroxol group (P = 0.011). The fluorescein corneal staining scores increased at 6 PM in both groups (P = 0.007 and P = 0.004, respectively), and they were higher in the ambroxol group compared with control group at 10 AM the next day (P = 0.035). The mean tear secretion did not show a significant change in the control group and increased at 10 AM the next day in the ambroxol group (P = 0.022). In both groups, the tear osmolality increased at 6 PM (P = 0.009 and P = 0.005, respectively), but the tear osmolality in the ambroxol group was higher compared with control group at 6 PM (P = 0.043). CONCLUSIONS:: Oral ambroxol may disturb tear film and ocular surfaces by attenuating the mucin layer of the tear film. This study was registered as Clinical Trial at ClinicalTrials.gov. as NCT01713179.
Cornea 03/2013; · 1.73 Impact Factor
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ABSTRACT: BACKGROUND: Intraocular CMV infections, including endotheliitis and retinitis, have been reported to threaten the host's vision. These infections have been treated with systemic or intravitreal GCV injection. Intracameral GCV injection can be an effective treatment option with avoiding the systemic side effect. The cytotoxic effect of ganciclovir (GCV) on cultured human corneal endothelial cells (HCECs) was evaluated. METHODS: HCECs were cultured and exposed to various concentrations (0-20 mg/mL) of GCV (Cytovene®, Roche, Colorado). Cell viability was assessed by the Cell Counting Kit-8 method and Live/Dead Viability/Cytotoxicity assays. Cell morphology was assessed using phase-contrast microscopy after 48 h exposure to GCV. Cell cycle and apoptosis were analyzed using NC-3000 to evaluate the effect of GCV on HCECs. The cell proliferation rate was evaluated by a BrdU proliferation assay. RESULTS: Cytotoxicity tests showed that GCV had a dose-dependent cytotoxic effect on HCECs. GCV concentrations of ≥ 5 mg/mL resulted in a significant reduction in cell viability. Higher concentrations of GCV resulted in cell cycle delay, low proliferation rate, and an increased number of apoptotic cells, indicating activation of the pro-apoptotic pathway. CONCLUSIONS: Our results suggest that intracameral GCV concentrations of ≥ 5 mg/mL may increase the risk of corneal endothelial damage, although GCV concentrations of ≤ 0.5 mg/mL do not decrease cell viability.
Antiviral therapy 03/2013; · 3.16 Impact Factor
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ABSTRACT: PURPOSE:: To determine the efficacy and safety of argon laser photocoagulation of pinguecula by evaluating 1-year outcomes. METHODS:: Twenty-one eyes of 15 patients treated with argon laser photocoagulation (photocoagulation group) and 23 eyes of 16 patients treated with surgical excision (excision group) were retrospectively reviewed. Cosmetic outcome was evaluated by patient's self-report on a 5-grade scale (excellent, good, acceptable, poor, and very poor), and evaluation of treatment outcome was based on objective findings of anterior segment photography and anterior segment optical coherence tomography. RESULTS:: Overall cosmetic results were excellent or good in 90.5% of laser-treated cases and 78.6% of surgically treated cases. There was no significant difference in cosmetic outcome (P = 0.15). Nineteen (90.5%) and 17 (63.9%) cases demonstrated complete removal of pingueculae after laser photocoagulation and surgical excision, respectively. The anatomic outcome was not significantly different between the 2 groups (P = 0.25). Subconjunctival hemorrhage and conjunctival scarring with an irregular surface occurred less frequently in the photocoagulation group than in the excision group [34.8% vs. 0% (P = 0.003) and 30.4% vs. 4.8% (P = 0.048), respectively]. CONCLUSIONS:: Argon laser photocoagulation is an effective and safe method for removing a pinguecula for cosmetic purposes. The method facilitates control of the extent and depth of removal and thus minimizes conjunctival defects and other complications.
Cornea 02/2013; · 1.73 Impact Factor
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ABSTRACT: To compare the effect of using fibrin glue or 10-0 nylon sutures on the clinical outcome of patients undergoing pterygium excision and conjunctival autografting.
We retrospectively reviewed the medical records of 52 eyes from 46 patients who underwent pterygium excision and conjunctival autografting and were followed up for more than 3 months. The operation duration, postoperative inflammation, complications, and recurrence rates were compared between groups of 20 patients (22 eyes) for whom fibrin glue was used (fibrin glue group) and 26 patients (30 eyes) for whom suturing was performed with 10-0 nylon (suture group) in pterygium excision and conjunctival autografting.
The operation duration was 27.71 (5.22) minutes in the fibrin glue group and 43.30 (8.18) minutes in the suture group (p = 0.000). Seven days after the operation, the fibrin glue group showed milder conjunctival inflammation than the suture group (p = 0.000). Postoperative complications and corneal recurrence rates were not statistically different between the two groups.
The use of fibrin glue in pterygium excision with conjunctival autografting is likely to be a more effective, safer procedure than suturing.
Korean Journal of Ophthalmology 12/2012; 26(6):407-13.
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ABSTRACT: BACKGROUND: To investigate the long-term results and visual outcomes of penetrating keratoplasty (PKP) in Peters anomaly. METHODS: Twenty-three eyes from 22 patients with Peters anomaly who underwent PKP from 1998 to 2008 were reviewed retrospectively. Patients who were followed for more than 3 years after the first PKP were included in this study. The systemic and ophthalmic features of the recipients were assessed, and the various prognostic factors for graft survival were evaluated. Disease severity was determined according to other accompanying eye anomalies in mild or severe form. The final visual outcomes were presented with respect to graft clarity. RESULTS: Among the 22 patients, 14 patients had unilateral disease, and eight patients had bilateral disease. Associated systemic anomalies were observed in six patients. The mean age at the first PKP was 42.4 months. Nineteen eyes (83 %) underwent PKP after 12 months of age. The graft failure rates at 1 year, 3 years, 5 years, and 10 years after PKP were 30 %, 39 %, 70 %, and 77 % respectively. Graft rejection within 1 month after PKP and severe disease were significant risk factors for graft failure. The mean final VAs in the clear-graft group and the failed-graft group were 1.883 logMAR and 2.767 logMAR (P < 0.001). CONCLUSION: The results of delayed PKP in Peters anomaly were not inferior compared to the results of PKP performed at an earlier period in previous studies. If other congenital ophthalmic anomalies were present or graft rejection occurred within 1 month after PKP, the chance of graft failure was significantly increased.
Albrecht von Graæes Archiv für Ophthalmologie 10/2012; · 2.17 Impact Factor
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ABSTRACT: The aim of this retrospective study was to identify factors affecting myopic shift from predicted values of refraction after sulcus fixation of foldable acrylic intraocular lenses (IOLs).
A total of 91 eyes from 91 consecutive patients, each of whom underwent primary implantation of sulcus-fixated foldable acrylic IOLs, were assessed. AcrySof MA60BM and Sensar AR40e multi-piece IOLs, and AcrySof SA60AT and BioVue single-piece IOLs were implanted. The type of IOL and axial length (AL) were analysed to identify differences in the spherical equivalent between the predicted refraction values obtained using the SRK/T formula and the manifested refraction values.
The mean myopic shift from the predicted refraction calculated using the SRK/T formula was -1.04 dioptres (D) ±0.85 SD with sulcus fixation of the foldable acrylic IOLs. The type of IOL (multi-piece vs single-piece) did not affect the degree of myopic shift (p=0.100, independent t-test). However, as the AL increased, the myopic shift decreased (p=0.033, r=0.223, Pearson's correlation).
The myopic shift from the predicted refraction differed following sulcus fixation of foldable acrylic IOLs based on the AL, and therefore surgeons should take the AL into account when they determine the IOL power for sulcus fixation procedures.
The British journal of ophthalmology 08/2012; 96(10):1316-9. · 2.92 Impact Factor
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Sooyoung Yoo,
Kee Hyuck Lee,
Hak Jong Lee,
Kyooseob Ha,
Cheong Lim,
Ho Jun Chin,
Jonghoar Yun,
Eun-Young Cho,
Eunja Chung,
Rong-Min Baek,
Chin Youb Chung, Won Ryang Wee,
Chul Hee Lee,
Hai-Seok Lee,
Nam-Soo Byeon,
Hee Hwang
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ABSTRACT: Seoul National University Bundang Hospital, which is the first Stage 7 hospital outside of North America, has adopted and utilized an innovative and emerging information technology system to improve the efficiency and quality of patient care. The objective of this paper is to briefly introduce the major components of the SNUBH information system and to describe our progress toward a next-generation hospital information system (HIS).
SNUBH opened in 2003 as a fully digital hospital by successfully launching a new HIS named BESTCare, "Bundang hospital Electronic System for Total Care". Subsequently, the system has been continuously improved with new applications, including close-loop medication administration (CLMA), clinical data warehouse (CDW), health information exchange (HIE), and disaster recovery (DR), which have resulted in the achievement of Stage 7 status.
The BESTCare system is an integrated system for a university hospital setting. BESTCare is mainly composed of three application domains: the core applications, an information infrastructure, and channel domains. The most critical and unique applications of the system, such as the electronic medical record (EMR), computerized physician order entry (CPOE), clinical decision support system (CDSS), CLMA, CDW, HIE, and DR applications, are described in detail.
Beyond our achievement of Stage 7 hospital status, we are currently developing a next-generation HIS with new goals of implementing infrastructure that is flexible and innovative, implementing a patient-centered system, and strengthening the IT capability to maximize the hospital value.
Healthcare informatics research. 06/2012; 18(2):145-52.
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ABSTRACT: To establish an in vitro model to study the role of keratocytes in corneal chemical burns and to investigate the interaction between chemically injured keratocytes and human peripheral blood mononuclear cells (PBMCs).
Human keratocytes, epithelial cells, and PBMCs were cultured. The PBMC stimulation assay was then performed using cultured human keratocytes, epithelial cells, and NaOH-treated keratocytes. Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-β1), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA.
Human keratocytes stimulated PBMC proliferation (p=0.016), and keratocytes treated with various concentrations of NaOH further stimulated PBMC proliferation compared to control cells in a dose-dependent manner (p=0.028 and 0.009). MMP-9 and MIF levels were higher than in the negative controls, while TGF-β1 levels did not differ from those of the negative controls.
Our results suggest that PBMCs are stimulated by chemically injured keratocytes, and produce inflammatory cytokines in response. This may be a major mechanism underlying the process causing corneal chemical burn injuries. This model can be used as an in vitro model for further studies on corneal chemical burns.
Cytokine 05/2012; 59(2):280-5. · 3.02 Impact Factor
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ABSTRACT: The visual system homeobox 1 (VSX1) gene variants have recently been shown to be associated with keratoconus. To replicate this finding, we performed a genetic analysis of the VSX1 gene in a Korean case-control sample.
Patients with keratoconus and healthy control subjects were recruited from Seoul National University Hospital. A diagnosis of keratoconus was made based on clinical examinations and the presence of characteristic topographic features. For all patients and controls, the whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing.
Fifty-three patients with keratoconus and 100 healthy volunteers were included. We observed 2 novel missense substitutions (Leu17Val and Val199Leu) and 1 previously reported substitution (Gly160Val) in 6 of the 53 affected probands. Because these substitutions have been identified in unaffected individuals, they were not considered to be pathogenic. No intragenic polymorphism was associated with a significantly increased risk of keratoconus.
We cannot confirm the previously reported association of the VSX1 gene variants with keratoconus. Our results suggest that the VSX1 gene and its mutations with amino acid changes do not play a major role in the pathogenesis of keratoconus.
Cornea 04/2012; 31(7):746-50. · 1.73 Impact Factor
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ABSTRACT: To determine the effect of intracamerally injected voriconazole on corneal endothelial cells in rabbit eyes.
Various concentrations of voriconazole (0%, 0.03%, 0.1%, 0.25%, 0.5% and 1%) were injected intracamerally in 36 eyes of 18 rabbits (six eyes for each concentration). Measurements of endothelial cell counts and central corneal thickness were performed at 30, 60, 90 and 120 min after the injection. In each group, five of six corneas were used for the live/dead cell assay; staining with alizarin red and trypan was done. In one cornea from each group, scanning electron microscopy was performed.
There was no significant difference in endothelial cell counts and central corneal thickness among the six groups at any time points. The live/dead cell assay revealed no difference in the mean percentage of dead endothelial cells among the six groups (p=0.504). However, scanning electron microscopy revealed blurring of cell border at voriconazole concentrations ≥ 0.25%, indicating cell wall damage.
Intracameral injection of voriconazole did not induce a significant gross change in rabbit corneal endothelial cells up to a concentration of 1%. However, risk of microstructural damages might exist with a concentration of ≥ 0.25%.
The British journal of ophthalmology 03/2012; 96(6):905-8. · 2.92 Impact Factor
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ABSTRACT: To investigate whether ethanol administration disturbs the tear film and ocular surface.
Case-control study.
Twenty healthy male subjects were recruited. Ethanol was administered to 10 subjects and another 10 subjects served as controls.
Twenty healthy male subjects with no ocular disease were recruited. Ethanol (0.75 g/kg) was administered orally at 8 pm for 2 hours to 10 subjects.
The tear film and ocular surface were evaluated at 6 pm before drinking, at midnight, and immediately (6 am) and 2 hours (8 am) after waking the next morning. Tear osmolarity, ethanol concentration in tears and serum, Schirmer's test results, tear film break-up time (TBUT), corneal punctuate erosion, and corneal sensitivity were measured.
Ethanol was detected in tears and serum at midnight, but it was not detected the next morning. The mean tear osmolarity level increased in the alcohol group at midnight compared with that in the control group (P<0.001). The alcohol group showed a significantly shorter TBUT compared with the control group after drinking alcohol (P<0.001 at 12 am, P<0.001 at 6 am, and P = 0.002 at 8 am). There were significantly higher fluorescein staining scores in the alcohol group compared with those in the control group at 6 am and 8 am (P = 0.001 and P<0.001, respectively). No significant change was shown in corneal sensitivity or Schirmer's test results in either group.
Orally administered ethanol was secreted into the tears. Ethanol in tears induced tear hyperosmolarity and shortened TBUT and triggered the development of ocular surface diseases. Similar changes could exacerbate signs and symptoms in patients with ocular surface disease.
Ophthalmology 02/2012; 119(5):965-71. · 5.45 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of limbal-conjunctival autografting with limbal fixation sutures after pterygium excision.
We retrospectively reviewed the records of 90 patients (103 eyes) who received limbal-conjunctival autografts with limbal fixation sutures after excision of the primary pterygium (82 eyes) and recurrent pterygium (21 eyes). ResuLTS: The study subjects comprised 41 male patients (47 eyes) and 49 female patients (56 eyes) with a mean age of 51.1 ± 10.5 years (range 32-77). The mean follow-up period was 18.9 ± 9.2 months (range 12-50). Among the 103 eyes, recurrence occurred in 2 eyes (1.9%) after 2 and 4 months, respectively. As complications, 1 case of conjunctival cyst and 2 cases of pseudopterygium at the donor site were reported.
Limbal-conjunctival autografting with limbal fixation sutures appears to be an effective and safe method of reducing the recurrence rate after pterygium excision.
Ophthalmologica 02/2012; 227(4):210-4. · 1.42 Impact Factor
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Canadian Journal of Ophthalmology 02/2012; 47(1):e1-2. · 1.47 Impact Factor
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Sang-Mok Lee,
Eui Man Jeong,
Jinho Jeong,
Dong-Myung Shin,
Hyun-Ju Lee,
Hyo-Jun Kim,
Jisun Lim,
Jin-Haeng Lee,
Sung-Yup Cho,
Mee-Kum Kim, Won-Ryang Wee,
Jin-Hak Lee,
In-Gyu Kim
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ABSTRACT: The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model.
Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined.
In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats.
Cysteamine suppresses cataract formation induced by selenite in rats, suggesting that cysteamine can be used as a pharmaceutical intervention to prevent or delay cataract formation.
Investigative ophthalmology & visual science 01/2012; 53(3):1452-9. · 3.43 Impact Factor
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Albrecht von Graæes Archiv für Ophthalmologie 01/2012; · 2.17 Impact Factor
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ABSTRACT: To report on the clinical and histopathologic findings of a conjunctival juvenile xanthogranuloma in an adult.
Case report and literature review.
A 43-year-old man developed 2 yellowish conjunctival lumps not associated with other ocular or systemic findings. A half-corneal diameter-sized main mass was located at the 2-o'clock position, and the other 1/8-corneal diameter-sized mass was located at the 4-o'clock position. The masses were vitelliform in appearance with poor supplying vessels. The masses were removed en bloc by conjunctivectomy. Cryotherapy was done along the excision margin. Histopathologic examination revealed dense infiltration by histiocytes with background of multiple lymphocytes and Touton giant cells. Immunohistochemical staining was positive for CD3 (T-cell marker) and CD68 (histiocytic marker) but negative for CD1a and S-100 (Langerhans cell marker).
Juvenile xanthogranuloma may present as conjunctival infiltrative masses in adults. Immunophenotyping is helpful in differentiating it from a more malignant lesion.
Cornea 01/2012; 31(4):447-9. · 1.73 Impact Factor
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ABSTRACT: To investigate the protective effect of rapamycin on oxidative stress-induced cell death of human corneal endothelial cells (HCECs).
HCECs were cultured according to previously published methods. With treatment of 0 mM or 5 mM of tert-butyl hydroperoxide (tBHP) with various concentrations (0, 25 and 50 nM) of rapamycin, reactive oxygen species (ROS) production was measured using an oxidation-sensitive fluorescent probe, 2'7'-dichlorofluorescin diacetate (DCFH-DA, USA) methods. Cell viability was assayed by the method of Cell Counting Kit-8 (CCK-8, Wako). The levels of cellular glutathione were also assessed enzymatically with glutathione reductase by using a commercial glutathione (GSH) assay kit (Cayman Chemical, USA).
Rapamycin reduced 2'7'-dihydrodichlorofluorescein oxidation and increased GSH in HCECs. Rapamycin significantly inhibited tBHP-induced ROS production. Cells treated with rapamycin showed higher viability compared to control at 5 mM tBHP. Rapamycin effectively protected HCECs from ROS-induced cell death through increasing intracellular GSH.
Our data suggest that rapamycin protects HCECs from oxidative injury-mediated cell death via inhibition of ROS production and enhancement of GSH.
Current eye research 12/2011; 36(12):1116-22. · 1.51 Impact Factor
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ABSTRACT: The potential of P-32 ophthalmic applicator irradiation after pterygium excision has been demonstrated as an alternative to Sr∕Y-90 irradiation. This study aimed to provide the clinical dosimetry for this new applicator.
The prototype of a cylindrical P-32 applicator was fabricated according to the Monte Carlo (MC)-based design study. At a nominal activity of 6 mCi (0.22 GBq), the absorbed dose rate at the front surface (i.e., reference dose rate) was measured by using an extrapolation ionization chamber (EC). The radiochromic film (RCF) was also used to measure the reference dose, axial depth dose distributions and transaxial dose profiles at various depths in water.
The reference dose rate was 3.89 ± 0.14 cGy∕s for EC and 3.84 ± 0.25 cGy∕s for RCF. The depth dose rate was reduced approximately by an order of magnitude for every 2 mm depth in water. Measured depth doses in depths of 0.5-2.5 mm agreed with Monte Carlo data within ±3%. Due to nonuniform absorption of P-32 into an absorbent disk, the dose profiles were not symmetric and decreased more rapidly toward the periphery than those predicted by the MC. The authors confirmed no leakage of P-32 activities and negligible exposure rate around the hand grip of the applicator.
The P-32 applicator can deliver therapeutic doses to the surface of the conjunctiva, while sparing the lens better than Sr∕Y-90 applicators. The doses at any points from the P-32 applicator could be calculated by using the measured dosimetry data. They also confirmed no leakage of the source, reliable integrity of the applicator, and negligible exposure level around the hand grip of the applicator. However, due to a possibility of nonuniform distributions of P-32 in an absorbent disk, measuring dose profiles as well as the reference dose rate for every new applicator would be recommended.
Medical Physics 11/2011; 38(11):6143-51. · 2.83 Impact Factor
