Stability of Bevacizumab Divided in Multiple Doses for Intravitreal Injection.

OBJECTIVE: To investigate the stability of bevacizumab in multiple doses divided from a single-use vial for intravitreal injection after storage at 4°C for up to six months and under drug transfer condition in tropical climate. MATERIAL AND METHOD: Five syringes (0.1 mL, 2.5 mg) of bevacizumab were withdrawn each from five new bevacizumab single-use vials (4 mL, 100 mg) under sterile technique. The concentration of bevacizumab in each syringe was measured at two dilutions (2 x 10(6) and 4 x 10(6) fold) using enzyme-linked immunosorbent assay at baseline and after storage at 4°C for 1-, 3-, and 6-month. Each assay was performed at least twice. To simulate the drug transfer condition, bevacizumab was placed in a brown plastic bag and put in another transfer plastic bag with an ice cube for 30 minutes prior to the assay at 1-, 3-, and 6-month. RESULTS: The concentrations of bevacizumab (mean ± standard deviation) at baseline, 1-, 3-, and 6-month were 26.24 ± 1.95, 25.43 ± 3.80, 27.87 ± 2.81, and 24.25 ± 2.00 mg/mL, respectively. The lowest lower limit of 95% confidence interval for the mean concentration was 23.32 mg/mL at 6-month storage, which was 89% of the mean baseline concentration and considered to be non-inferior to the baseline concentration. CONCLUSION: Bevacizumab in a single-use vial could be divided into multiple small doses for intravitreal injection with sufficient stability when refrigerated at 4°C for up to six months and under the drug transfer condition in tropical climate.

Enhanced depth imaging spectral-domain optical coherence tomography of the choroid in Thai population.

OBJECTIVE: To examine subfoveal choroidal thickness (SFCT) in Thai population using enhanced depth imaging spectral- domain optical coherence tomography (EDI-OCT) and to study its correlation with foveal retinal pigment epithelium thickness (FRPE), central neurosensory retinal thickness (CNRT), age, and refraction. MATERIAL AND METHOD: Four hundred eighty eyes from 240 subjects without glaucoma, retinal, or choroidal diseases underwent scanning of the retina and choroid using EDI-OCT SFCT FRPE, and CNRT measurements were based on the 1:1 micron images and wereperformed by two independent observers. The reliability ofmeasurements between the observers was evaluated by intraclass correlation coefficient (ICC). The correlations of SFCT with FRPE, CNRT, age, and refractive error were analyzed RESULTS: The mean age of the subjects was 36.22 years (range 20-81years). The means (95% reference intervals) of SFCT, CNRT andFRPE were 294.02 µm (137.14-450.90 µm), 174.22 µm (141.82-206.62 µm), and 41.94 µm (34.65-49.23 µm), respectively. SFCT and CNRThad excellent reliability between the two observers [ICC = 0.947 (95% CI, 0.918-0.963) and 0.929 (95% CI, 0.906-0.945), respectively], while FRPE showed good reliability [ICC = 0. 729 (95% CI, 0.637-0.793)]. SFCT had a low positive correlation with FRPE (r = 0.179, p<0. 0001) but not with CNRT (p = 0.317). SFCT showed a positive correlation with refraction (r = 0.338, p<0.0001) and a negative correlation with age (r = -0.166, p<0.0001). Regression analysis suggested that the SFCT decreased by 12.23 pm per one decade oflife and by 11.42 pm per one diopter of myopia. CONCLUSION: Normal values of SFCT in Thai population were obtained SFCT significantly decreased with older age and higher myopia. SFCT was associated with FRPE, reflecting the same vascular supply of the choroid and retinal pigment epithelium. When measured with our technique based on the 1:1 micron images, the reliability ofSFCT measurement was very high despite highly morphologic inter-individual variations.

Optic atrophy after anti-vascular endothelial growth factor injection in diabetic patients with proliferative diabetic retinopathy.

OBJECTIVE: To study the prevalence of optic atrophy in patients with proliferative diabetic retinopathy (PDR) who underwent intravitreal bevacizumab injection and risk factors associated with optic atrophy. MATERIAL AND METHOD: A retrospective case control study enrolled 269 cases (394 eyes) of patients with PDR, in which 166 cases (219 eyes) received intravitreal bevacizumab injection. Associated factors such as type of DM, hemoglobin A1c level, hypertension, hypercholesterolemia, chronic kidney disease, previous intravitreal surgery retinal detachment, and vitreous hemorrhage were recorded. Criteria for diagnosis of optic atrophy were decreased visual acuity, pale optic disc and decreased nerve fiber layer thickness, which was measured by Stratus optical coherence tomography (OCT). The association between intravitreal bevacizumab injection and optic atrophy was analyzed by multiple logistic regression. RESULTS: Two hundred sixty nine patients with PDR, consisting of 166 patients with intravitreal bevacizumab injection and 103 cases without bevacizumab injection. Optic atrophy was found in 11.4% (25/219 eyes) and 8% (14/175 eyes) respectively. There was no evidence that intravitreal bevacizumab injection and associated systemic diseases were related to optic atrophy. The risk factor that was related to optic atrophy was previous intravitreal surgery (adjusted odds ratio (OR), 2.57 [95% CI, 1.13, 5.84], p = 0.024). CONCLUSION: Anti-VEGF (bevacizumab) does not increase the risk of optic atrophy. The ophthalmologists should be aware of subsequent optic atrophy development in patients with PDR who undergo surgical intervention.

Causes of visual impairment in Thai diabetic patients in the visual rehabilitation clinic.

BACKGROUND: Visual disability from diabetic retinopathy is one of many public health problems. Knowing the causes of blindness and low vision in diabetic patients will help in policy planning in order to reduce diabetic complications and prevent blindness. OBJECTIVE: To study the causes of visual impairment, blindness and related factors in diabetic patients who registered at the visual rehabilitation clinic, Siriraj Hospital, Mahidol University, Bangkok. MATERIAL AND METHOD: A retrospective study of 133 diabetic patients who registered at the visual rehabilitation clinic between January 2007 and December 2010 was conducted. The patients were divided into 2 groups: a low vision group (VA in the better eye < 6/18-3/60) and a blindness group (VA in the better eye < 3/60--No light perception). The history of diabetic mellitus, associated systemic diseases, laboratory investigations, ocular changes and treatment were recorded. The causes of visual impairment and blindness were collected and analyzed. RESULTS: Of a total of 133 diabetic patients, 93 cases (69.9%) were in a low vision group and 40 cases (30.1%) were in a blindness group. The causes of visual impairment were proliferative diabetic retinopathy (84.6%), retinal detachment (37.2%), macular edema and scar (25.9%), optic atrophy (143%), neovascular glaucoma (11.7%) and vitreous hemorrhage (4.9%). Tractional retinal detachment (p-value < 0.001) and optic atrophy (p-value = 0.021) were the associated factors causing blindness in visual disability patients with statistical significance. Optic atrophy (38 eyes) occurred post vitrectomy in 19 eyes. CONCLUSION: Visual disability in diabetic patients is caused by the complications of diabetic retinopathy and its management. The prevention of disease progression, especially macular edema and proliferative diabetic retinopathy, will decrease the rate of visual impairment and blindness.

Nonmydriatic digital retinal images for determining diabetic retinopathy.

OBJECTIVE: To evaluate the efficacy of nonmydriatic digital retinal images for determining diabetic retinopathy. MATERIAL AND METHOD: Single field 45-degree digital retinal images of 225 eyes from 142 diabetic patients were obtained with a nonmydriatic camera. The images were diagnosed and graded by a general ophthalmologist. These results were compared with clinical diagnosis obtained by retinal specialists, after examination by using biomicroscope with plus lens and indirect ophthalmoscope of the patients. International clinical diabetic retinopathy disease severity scale was used for grading diabetic retinopathy in all cases. RESULTS: Presence of diabetic retinopathy was detected in 70 eyes (31.1%). The sensitivity and specificity for determining diabetic retinopathy was 68.57% (95%CI 57.00-78.20) and 92.25% (95%CI 87.00-95.50), respectively. The positive predictive value and negative predictive value was 80.00% (95%CI 68.20-88.20) and 86.67% (95%CI 80.60-91.00). Overall accuracy was 84.89%. CONCLUSION: Single field 45-degree nonmydriatic digital retinal images were limited by fair sensitivity for determining diabetic retinopathy although overall accuracy from the present study was relatively high. Upcountry, this tool might facilitate increased access of diabetic patients for eye evaluation but cannot replace standard eye examination.