Intravitreal bevacizumab for the treatment of refractory diabetic macular edema.

BACKGROUND AND OBJECTIVE: To report the effect of intravitreal bevacizumab on visual acuity and central retinal thickness (CRT) in refractory diabetic macular edema. PATIENTS AND METHODS: Records of 60 eyes of 54 consecutive patients who underwent intravitreal bevacizumab therapy for refractory diabetic macular edema were reviewed. All eyes received intravitreal bevacizumab 1.25 mg/0.05 mL, and 36 eyes underwent pretreatment and post-treatment optical coherence tomography. Mean follow-up was 7.4 months. RESULTS: Pretreatment mean visual acuity plus or minus standard deviation was 0.71 +/- 0.28 logarithm of the minimum angle of resolution (LogMAR) Snellen letters. At final follow-up, mean visual acuity had improved to 0.66 +/- 0.30 LogMAR (P = .0543). Mean baseline CRT was 440 +/- 106 microm, and follow-up mean CRT was 386 +/- 129 microm (P = .008). Vitrectomized eyes had worse visual acuity and CRT outcomes (P = .002 and P = .028, respectively) compared with nonvitrectomized eyes. CONCLUSION: Intravitreal bevacizumab may provide a functional and anatomic benefit in eyes with persistent diabetic macular edema despite previous treatments.

Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy.

AIM: To determine whether there is an association between complement factor H (CFH) or LOC387715 genotypes and response to treatment with photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: Sixty-nine patients being treated for neovascular AMD with PDT were genotyped for the CFH Y402H and LOC387715 A69S polymorphisms by allele-specific digestion of PCR products. AMD phenotypes were characterized by clinical examination, fundus photography, and fluorescein angiography. RESULTS: Adjusting for age, pre-PDT visual acuity (VA), and lesion type, mean VA after PDT was significantly worse for the CFH TT genotype than for the TC or CC genotypes (P=0.05). Post-PDT VA was significantly worse for the CFH TT genotype in the subgroup of patients with predominantly classic choroidal neovascular lesions (P=0.04), but not for the patients with occult lesions (P=0.22). For the LOC387715 A69S variant, there was no significant difference among the genotypes in response to PDT therapy. CONCLUSIONS: The CFH Y402H variant was associated with a response to PDT treatment in this study. Patients with the CFH TT genotype fared significantly worse with PDT than did those with the CFH TC and CC genotypes, suggesting a potential relationship between CFH genotype and response to PDT.

Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab.

AIMS: To determine whether complement factor H (CFH) genotypes have a pharmacogenetic effect on the treatment of exudative age-related macular degeneration (AMD) with ranibizumab. METHODS: A retrospective study of 156 patients with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. AMD phenotypes were characterised by clinical examination, visual acuity, fundus photography, fluorescein angiography and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmological care and were followed for a minimum of 9 months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene. RESULTS: Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional ranibizumab injections (p = 0.04). CONCLUSIONS: In this study cohort, the response to treatment of AMD with ranibizumab differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal ranibizumab.

Anatomy of a meta-analysis: a critical review of "exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance".

BACKGROUND: Accurate diagnosis of coronary heart disease has the potential to contribute substantially to cost-effective delivery of health services. Recent work by Fleischmann et al (JAMA 1998;280:913-20) represents an effort to summarize the accuracy of exercise echocardiography and exercise single photon emission computed tomography (SPECT). METHODS AND RESULTS: A critique of the previous work was constructed, obtaining the 44 articles used. These articles were reviewed and summarized with established techniques for meta-analysis. The studies summarized by Fleischmann et al were found to be significantly heterogeneous (echocardiography and SPECT, both P<.001). In the SPECT cohort, combination of different radioisotopes and reading techniques, and inclusion of reports using experimental techniques, were sources of heterogeneity. In the echocardiography cohort, experimental techniques and an individual series were identified. When the sample was stratified for sources of heterogeneity, it was found that there was no significant difference in diagnostic accuracy between the echocardiography and SPECT techniques used in current clinical practice. Meta-regression with summary receiver operating characteristic curve techniques, after adjustment of the model for multicolinearity and outliers, revealed that there were no significant differences between SPECT as used in current clinical practice and echocardiography. CONCLUSION: The report by Fleischmann et al contains serious flaws that limit its validity and generalizability.