Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child.

PURPOSE: To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165. METHODS: A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF. RESULTS: Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection. CONCLUSIONS: These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.

Second eye of patients with unilateral neovascular age-related macular degeneration: Caucasians vs Chinese.

PURPOSE: To investigate the correlation between morphological features of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) in the first eye and the severity of age-related maculopathy (ARM) in the fellow eyes in two racial groups: Caucasians and Chinese. PARTICIPANTS: A total of 135, fluorescein angiograms of patients with unilateral neovascular AMD and ARM in the fellow eyes were included in the study: 38 Caucasians from King's College Hospital, UK; 45 Caucasians from West Kent Eye Centre, UK; 52 Chinese from Hong Kong Eye Hospital, Hong Kong. MAIN OUTCOME MEASURES: CNV subtype in the affected eye and ARM severity in the second eyes. RESULTS: Although the proportion of CNV subtypes in the three groups were similar, the Chinese cohort showed significantly less ARM severity compared to the Caucasian cohorts (P < 0.05). CONCLUSION: Although drusen and retinal pigmentary changes may be prognostic indicators of CNV, this study suggest that other factors contribute significantly to the pathogenesis of CNV in AMD.

Drusen classification in bilateral drusen and fellow eye of exudative age-related macular degeneration.

AIM: To assess the value of the modified international classification system in screening high-risk patients with bilateral age-related maculopathy (ARM) from those with lower risk characteristics. METHODS: In total, 164 digital images of 106 patients with either bilateral ARM (group A) or the fellow eyes of unilateral exudative age-related macular degeneration (AMD) (Group B) were included. Patients with no signs of ARM in both eyes or those with bilateral late AMD were excluded. The images were randomised and then graded by two masked ophthalmologists based on the modified International Classification of ARM. RESULTS: The interobserver consistency between the two graders was high with a Kappa value of 0.82 (SE 0.34, P<0.0001). There were no significant differences in the distribution of the stages of ARM between the two subgroups. Stage 3 was the most common stage in each group for both graders followed by stage 2a in the bilateral drusen group. Stages 1a, 2a and 2b were equally the next common stage in the fellow eye of chordial neovascularisation group. CONCLUSION: A screening system based on clinical characteristics would be of value in risk prediction in a clinical setting. Type of Drusen alone, as identified by the modified International grading system, may not be reliably predictive in screening for patients who are at high risk of developing choroidal neovascularisation.

An interinstitutional comparative study and validation of computer aided drusen quantification.

AIMS: To assess the portability and clinical applicability of a software program based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen quantification. METHODS: Independent graders from the Digital Fundus Photo Reading Center of Columbia University and King's College Hospital used macular background levelling software to quantify the percentage of drusen in the central and middle Wisconsin subfields. 100 images of consecutive patients with choroidal neovascularisation in one eye and significant drusen in the other eye were analysed to determine suitability, and 10 were chosen for assessment by this software. RESULTS: Of the 10 images used in the interinstitutional validation, the random effects ANOVA for the central and middle subfields showed a high degree of interobserver agreement. The ICC for interobserver reliability was 0.83 (95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the middle subfield. Overall agreement with the manual grading results was good and the within patient coefficient of variation was about 20% for all the pairwise comparisons between observers and the manual stereo gradings. Of the 100 images used to assess practical applicability of the software, 79 were suitable for semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE) changes limiting drusen identification, five had a significant number of reticular drusen, which are poorly identified by the software, and three had multiple small areas of RPE atrophy, which are difficult to distinguish from drusen. CONCLUSIONS: The software was successfully used by two institutions demonstrating portability, with good correlation between graders and to the manual stereo grading. Digital drusen quantification was possible in 79% of the images analysed.

Diode laser trans-scleral cyclophotocoagulation in the management of glaucoma in patients with long-term intravitreal silicone oil.

AIMS: To analyse the results of contact trans-scleral cyclodiode photocoagulation (TSCPC) in reducing intraocular pressures (IOP) refractory to medical treatment in a group of patients with intravitreal silicone oil. METHODS: The medical records of 18 patients who received TSCPC were evaluated retrospectively. Success was evaluated primarily in terms of IOP control. Success was defined as a final IOP of less than 22 mmHg. RESULTS: In all, 18 eyes of 18 patients were followed up for an average of 21.8 months (range 6-36) (SD=8.6). The mean pre-treatment IOP was 39.6 mmHg (range 25-56 mmHg) (SD=9.3). This reduced to 20.0 mmHg (range 0-48, SD=13.5) after TSCPC, producing a mean reduction of 49% from mean pretreatment IOP levels. The overall success rate was 44% (eight eyes). Chronic hypotony occurred in two patients. IOP remained above that required to meet the IOP reduction criteria in eight patients. CONCLUSION: Our results raise doubts about the efficacy of TSCPC in the management of glaucoma in eyes retaining silicone oil. This may relate to the long duration of silicone oil in our patients. Further studies are required to identify risk factors for treatment failure.

Radiotherapy for neovascular age-related macular degeneration.

BACKGROUND: Radiotherapy has been proposed as a treatment to prevent new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: The aim of this review was to examine the effects of radiotherapy on neovascular AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library Issue 2, 2004, MEDLINE (1966 to May 2004), EMBASE (1980 to June 2004) and LILACS (Latin American and Caribbean Health Sciences Literature Database) (May 2004). We also wrote to investigators of trials included in the review to ask if they were aware of any other studies. SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with subfoveal choroidal neovascularisation secondary to AMD. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data. Relative risks were combined using a random effects model. The percentage of the variability in effect estimates that was due to heterogeneity, rather than sampling error, was estimated using I2. MAIN RESULTS: Eleven trials randomising a total of 1078 people were included in this review. All trials used a similar method of delivering the radiotherapy treatment (external beam). Dosage ranged from 7.5 to 24 Gy. Most trials found effects (not always significant) that favoured treatment. However, there was considerable inconsistency in the results between trials (I2 > 50%). As only 11 trials were included in the review and only some of these trials provided data for each outcome our ability to determine the causes of the heterogeneity between trials was limited. Subgroup analyses did not reveal any statistically significant interactions although with small numbers of trials in each subgroup (range two to four) this was not surprising. There was some indication that trials with no sham irradiation reported a greater effect of treatment as did trials with a greater percentage of participants with classic choroidal neovascularisation. REVIEWERS' CONCLUSIONS: This review currently does not provide evidence that external beam radiotherapy is an effective treatment for neovascular AMD. If further trials are to be considered to evaluate radiotherapy in AMD then adequate masking of the control group must be considered. Given the recent evidence that most lesions are amenable to treatment with photodynamic therapy if identified at a small lesion size, trials evaluating radiotherapy against photodynamic therapy are warranted.