Ling Yeung

Long-Term Tolerability and Serum Concentration of Bevacizumab (Avastin) when Injected in Newborn Rabbit Eyes

PURPOSE. To test the long-term effects and systemic exposure level after single or multiple bevacizumab (Avastin) intravitreal injections in newborn rabbit eyes. METHODS. Four groups of newborn New Zealand rabbits received a single intravitreal bevacizumab injection at a concentration of 1.25 mg/0.05 mL at the ages of 2 (group 1), 4 (group 2), 6 (group 3), and 12 (group 5) weeks. The other group of rabbits (group 4) received three consecutive injections of bevacizumab at a concentration of 1.25 mg/0.05 mL at weeks 2, 6, and 10. Eight days after injection, the serum concentration of bevacizumab was determined in groups 1, 2, 3, and 5. Morphologic and functional changes were evaluated 12 months after bevacizumab injection. RESULTS. Twelve months after either single or multiple intravitreal injections of bevacizumab, newborn rabbit eyes showed no significant differences compared with control eyes on examination with funduscopy, histopathology, or electroretinogram. The serum concentrations when the injections were performed at the ages of 2 (19.4 +/- 8.1 microg/mL) and 4 (10.2 +/- 2.3 microg/mL) weeks were significantly higher than the serum level detected when the injection was performed at 12 weeks of age (2.8 +/- 1.2 microg/mL, P = 0.02 and P = 0.024, respectively). CONCLUSIONS. After 1 year, single and three consecutive intravitreal injections of 1.25 mg bevacizumab in newborn rabbit eyes are well tolerated. Systemic exposure is higher when the injection is performed at an early age.

Traumatic Pediatric Retinal Detachment following Open Globe Injury

Purpose: It was the aim of this study to describe the clinical features and surgical outcomes of retinal detachment following open globe injuries in a pediatric population. Methods: The study was a retrospective chart review of 33 children who had undergone surgery for retinal detachment after open globe injury. Results: The mean age was 11 years (range 4–18) and the mean follow-up period was 57.1 months (range 6–204). Twenty-five patients (76%) were males. Of the open globe injuries, 21 (64%) were penetrations, 6 (18%) intraocular foreign bodies, and 6 (18%) ruptures. Eighteen retinal detachments (55%) were identified by B-scan. Eighteen eyes (55%) had total retinal detachment and 23 eyes (70%) showed macular involvement. Twenty-one eyes (64%) presented with proliferative vitreoretinopathy (PVR) grade C or worse. Retinal reattachment was successful in 12 eyes (36%). Best-corrected visual acuity of 20/100 or better was noted in 4 eyes (12%) preoperatively and in 12 eyes (35%) postoperatively. Features seen in patients with a poor surgical outcome included undetermined or light perception only preoperative vision (p = 0.012), diagnosis by B-scan (p = 0.003), the presence of PVR grade C or worse (p = 0.001), total retinal detachment (p = 0.001), and macula-off status (p = 0.016). Conclusions: Our findings suggest that retinal detachment caused by open globe injuries in the pediatric population is associated with worse surgical results and unsatisfied visual outcomes. Early vitrectomy, before a diagnosis of retinal detachment is made by serial echographic examinations, may be considered to reduce the incidence of PVR. Further clinical research is required to identify ways to improve the outcomes for these patients.

Reducing the incidence of early postoperative vitreous haemorrhage by preoperative intravitreal bevacizumab in vitrectomy for diabetic tractional retinal detachment

Acta Ophthalmol. 2010: 88: 635–640

Severe vitreous hemorrhage associated with closed-globe injury

BackgroundThe presence of marked vitreous hemorrhage is associated with poor visual prognosis in ocular trauma involving the posterior segment. The purpose of this study was to investigate the clinical features, prognostic factors, and visual outcomes in such eyes after closed-globe injury.MethodsRetrospective chart review of patients with severe vitreous hemorrhage after closed-globe injury between January 2000 and December 2002.ResultsThe study included 33 eyes in 32 patients with a mean age of 41.5 (range, 3–78 years) and a median follow-up period of 12 (range, 3–50 months). Presenting visual acuity was between 4/200, and there was light perception in 32 eyes (97%) and no light perception in one eye (3%). Fifteen eyes (45%) had one or more posterior segment pathologies beneath the vitreous hemorrhage. There were retinal tears in six eyes (18%), retinal detachment in six (18%), submacular hemorrhage in six (15%), choroidal rupture in three (9%), macular pucker in three (9%), retinal dialysis in one (3%), macular hole in one (3%), and retinal vessels occlusion in one (3%). Seven eyes (21%) had final visual acuity 20/40 or better, and 18 eyes (54%) had less than 20/200. Poor prognostic factors included presenting visual acuity of light perception or lower (p=0.032), hyphema (p=0.007), traumatic cataract (p=0.027), and age 55 years or younger (p=0.039). The most common cause of poor visual outcome was macular scar.ConclusionThe visual prognosis of severe vitreous hemorrhage after closed-globe injury was guarded. This was frequently associated with various anterior and posterior segment pathologies. In order to provide early visual rehabilitation and management of any potentially treatable posterior pathology, early vitrectomy may be considered.

Pediatric herpes simplex virus keratitis.

Purpose: To report the clinical characteristics and visual outcomes of pediatric herpes simplex virus (HSV) keratitis. Methods: The medical records of 29 patients younger than 16 years with HSV keratitis who were diagnosed and treated at Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1996 and 2004 were retrospectively reviewed. The diagnosis of HSV keratitis was proven by a positive viral culture and/or real-time quantitative polymerase chain reaction or by a clear history of dendritic keratitis or herpetic kerato-uveitis. Type of HSV keratitis, recurrence rate, and visual outcome were analyzed. Results: The average age at the entry into the study was 5.7 years (range: 7 months to 15 years). Mean follow-up time was 35.3 months (range: 2-69 months). Epithelial keratitis including dendritic and geographic ulcers was noted in 14 eyes, stromal keratitis in 2 eyes, stromal keratitis concurrent with epithelial keratitis in 8 eyes, and endotheliitis in 6 eyes. One patient had sequential involvement of both eyes. Thirteen patients (45%) developed recurrent HSV keratitis after the first documented episode. Female gender (but not age or the type of keratitis) was significantly associated with recurrences. Five patients who were maintained on oral valacyclovir prophylaxis up to 1 year had no recurrence during the period. Fifteen of 21 patients younger than 8 years of age had best-corrected visual acuity available at last follow-up, and 10 patients developed amblyopia. Conclusions: Children with HSV keratitis are at risk for recurrent keratitis and amblyopia. Prolonged systemic antiviral prophylaxis may help to prevent such consequences.

CENTRAL RETINAL VEIN OCCLUSION IN A YOUNG CHINESE POPULATION: Risk Factors and Associated Morbidity and Mortality

Purpose: The purpose of this study was to assess the risk factors for central retinal vein occlusion and associated morbidity and mortality in a Chinese population. Methods: The participants included patients with central retinal vein occlusion 40 years old and younger. Predisposing factors, mortality, and systemic complications were examined in this group. Results: Unilateral (n = 19) and bilateral (n = 3) central retinal vein occlusions were identified in a total of 22 patients (25 eyes), with a mean follow-up time of 37 months. Hypercholesterolemia (65%), hypertriglyceridemia (64%), and hyperhomocysteinemia (42%) were all identified as risk factors. Three patients (14%) developed stroke and 1 (5%) developed transient ischemic attacks during follow-up. Renal failure and pulmonary hypertension resulted in the death of two patients. The mean initial and final visual acuities (±standard deviation) were 20/400 (±20/250) and 20/500 (±20/320), respectively, and treatments did not result in vision improvement (P = 0.57). The poor visual prognosis was likely due to macular edema in 7 eyes (28%), optic atrophy in 4 eyes (16%), and secondary glaucoma in 3 eyes (12%). Conclusion: Morbidity and mortality are high in young Chinese patients with central retinal vein occlusion who may have associated serious complications including stroke, blindness, and death. Central retinal vein occlusion may serve as an initial clinical presentation of serious systemic diseases.

Secondary Ocular Hypertension After Intravitreal Injection with 2 mg or 4 mg of Triamcinolone in Retinal Vein Occlusion

PURPOSE To evaluate secondary ocular hypertension after intravitreal injection of triamcinolone acetonide (IVTA) with 2 mg/0.05 mL or 4 mg/0.1 mL for macular edema associated with retinal vein occlusion (RVO). METHODS A retrospective chart review was performed. Patients with RVO, including central RVO and branch RVO, were divided into 2 groups. Group 1 was patients who received 2 mg IVTA and group 2 received 4 mg IVTA. The dose of IVTA was dependent on individual surgeons decision. Secondary ocular hypertension was defined as intraocular pressure (IOP) >21 mmHg. Long-term antiglaucoma medication referred to eyes that required antiglaucoma agents for >6 months. RESULTS Thirty-six eyes in group 1 and 32 eyes in group 2 were included in the analyses. The mean age of all the patients was 58.6 years, and 52.9% of patients were men. The mean follow-up period was 12.4 months. A wide range (from day 7 to month 8) of time until the onset of the IOP spike was recorded after the injection. The incidence of secondary ocular hypertension was not significantly different between group 2 and group 1 (38.9% vs. 50%, P = 0.36). However, group 2 had a higher proportion of long-term antiglaucoma medication usage than group 1 (5.6% vs. 40.6%; Pearson chi-square, P < 0.001). Ultimately, 2.9% of patients underwent filtration surgery. Macular edema diminished and best-corrected visual acuity improved at 3 months later in both groups. CONCLUSIONS With a similar effect on vision recovery and alleviating macular edema associated with RVO, 2 mg IVTA required a shorter duration of medical control for secondary ocular hypertension than 4 mg IVTA.

Predictive factors for visual outcome to intravitreal bevacizumab in young Chinese patients with myopic choroidal neovascularization.

Purpose: To report the anatomical and functional outcomes of intravitreal bevacizumab in both young and old Chinese patients with myopic choroidal neovascularization. Methods: Consecutive series of 56 eyes (52 patients) with myopic choroidal neovascularization treated exclusively with intravitreal bevacizumab were reviewed retrospectively. Data from clinical examination, fundus photography, fluorescein angiography, and optical coherence tomography were collected. Results: Vision significantly improved after intravitreal bevacizumab in this patient series (P < 0.0001), with an average of 2.2 injections. Higher myopia was positively correlated to a worse outcome (r = –0.3, P = 0.036). Stratifying by age, the correlation between spherical equivalent and final outcome showed statistical significance (r = –0.44, P = 0.027) only in younger patients. In younger patients, both spherical equivalent (P = 0.036) and initial visual acuity (P = 0.004) were predictive factors for visual outcome after adjusting for age, spherical equivalent, and number of injections, whereas in older patients, only initial visual acuity (P < 0.0001) was predictive of visual outcome after similar adjustments. Conclusion: Younger patients do not have a better outcome when compared with older patients. Initial visual acuity, regardless of age, plays a more significant role. Both initial visual acuity and spherical equivalent are predictive factors for final visual acuity in young Chinese patients.

Serum concentration of bevacizumab after intravitreal injection in experimental branch retinal vein occlusion.

Aim: To compare the serum concentration of bevacizumab after intravitreal injection of bevacizumab (IVB) in an experimental model of branch retinal vein occlusion (BRVO) with control injections in albino rats. Methods: BRVO was created in one eye of each of the 24 albino rats. Another 24 rats served as controls. The BRVO was generated by argon laser photothrombosis after intravenous injection with Rose Bengal. Three days later, IVB (5 µl) was administered to both BRVO and control eyes. The serum concentration of bevacizumab was examined at baseline, 6 h, 1 day, 3 days, 7 days, 14 days, and 28 days after IVB. Results: At baseline, no serum bevacizumab was detected in either group. The serum concentration of bevacizumab reached a peak concentration at 1 day with 5,020 ± 1,602 ng/ml in the BRVO group and 4,103 ± 1,790 ng/ml in the control group (p < 0.001). The concentration decreased subsequently on days 3, 7, 14 and 28. The serum concentration of bevacizumab was significantly higher in BRVO rats up to 28 days after IVB. Conclusions: The serum concentration of bevacizumab after IVB reached its peak on day 1 in both BRVO and control eyes. This value was significantly higher in BRVO rats than in control rats up to 28 days after intravitreal injection.

Association of severity of conjunctival and corneal calcification with all-cause 1-year mortality in maintenance haemodialysis patients

BACKGROUND Conjunctival and corneal calcification (CCC) is the most common form of metastatic calcification in patients with chronic renal failure. The aim of this study is to investigate if severity of CCC correlates with vascular calcification and mortality in maintenance haemodialysis (MHD) patients. METHODS One hundred and nine MHD patients were recruited. CCC was evaluated by external eye photographs, and was graded and scored according to modified Porter and Crombie classification system described by Tokuyama et al. Chest X-ray examination was used to evaluate aortic arch calcification. Geographic, haematological, biochemical and dialysis-related data were obtained. The patients were analysed for traditional and non-traditional risk factors for cardiovascular disease stratified by severity of CCC. All patients were followed up for 1 year to investigate the risks for mortality. RESULTS Forty-three, 35 and 31 patients had mild (scores ≤ 4), moderate and severe (scores ≥ 9) CCC at baseline, respectively. With trend estimation, patients with severe CCC had a significantly higher percentage of severe aortic arch calcification. Multiple linear regression analysis showed that hypertension, haemodialysis duration and corrected calcium level were associated with scores of CCC in MHD patients. Moreover, age, corrected calcium-phosphate level, and moderate and severe CCC were associated with grades of aortic arch calcification. At 1-year follow-up, 11 of 109 (10.1%) patients had died. Multivariate Cox proportional hazards model showed that age, corrected calcium and severe CCC were significant risk factors for all-cause 1-year mortality in MHD patients. Each increment of one score of CCC is associated with a 26.4% increased risk for all-cause mortality. CONCLUSIONS Severity of CCC, which is easily obtained at bedside, acts as an independent predictor for all-cause 1-year mortality in MHD patients.