Interleukin-8 promoter polymorphism -251A/T is a risk factor for age-related macular degeneration.

BACKGROUND/AIMS: To determine whether four expression-related cytokine polymorphisms are associated with age-related macular degeneration (AMD). METHODS: DNA from 478 cases with AMD and 555 normal controls was genotyped for the pro-inflammatory IL1beta -511C/T, IL6 -174C/G, IL8 -251A/T and anti-inflammatory IL10 -1082G/A cytokine polymorphisms using the 5' nuclease TaqMan(R) assay for allelic discrimination. Associations with AMD were analysed using allelic frequencies. RESULTS: The -251A allele of the IL8 promoter gene polymorphism was more prevalent in AMD patients than controls (p = 0.037, OR = 1.21, 95% CI = 1.01 to 1.44). Adjusting for age, sex, body mass index (BMI), current smoking and past smoking status did not alter the AMD association significantly (corrected p value = 0.043, OR = 1.23, 95% CI = 1.0 to 1.50). CONCLUSION: The pro-inflammatory homozygous IL8 -251AA genotype is an important risk factor for AMD. This may have implications for future therapy with biological agents that could target this cytokine.

An analysis of the CFH Y402H genotype in AMD patients and controls from the UK, and response to PDT treatment.

AIM: Mutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV. METHODS: A total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 5' nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT. RESULTS: The risk association for AMD with the CFH CC genotype (odd ratio (OR)=3.62, Pc<0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs=4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR=17.87, P<0.0001) and CT (OR=9.06, P=0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR=2.16, P=0.011), and presence of the CC genotype significantly increased the risk of PDT (OR=5.48, P=0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P=0.038); 50% of CC cases (n=13) and 45% of the CT cases (n=12) lost 15 or more ETDRS letters at final follow-up. CONCLUSION: In this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.

Submacular haemorrhages after intravitreal bevacizumab for large occult choroidal neovascularisation in age-related macular degeneration.

OBJECTIVE: To report the occurrence of submacular haemorrhages following intravitreal bevacizumab for occult choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). METHODS: Retrospective chart review of 53 patients with occult CNV who had received intravitreal bevacizumab 1.25 mg. Analysis was done in three groups based on mean CNV lesion size: <10 mm(2) (n = 17), >/=10 to <15 mm(2) (n = 17) and >/=15 mm(2) (n = 18). ETDRS derived acuity, incidence of fresh macular haemorrhages and haemorrhage size (pre-existing or fresh) were documented and analysed. RESULTS: The median injection number was 1.0 (range: 1 to 3) with a minimum follow-up of 6 months (range: 4 to 12 months). The mean presenting size of occult lesions was 13.4 mm(2) (range: 3.0 to 30.3 mm(2)). Submacular fresh haemorrhages were seen in the absence of pre-existing haemorrhage in four out of 10 patients in the >/=15 mm(2) CNV size group (40%) but none in the remaining groups with CNV sizes <15 mm(2) (OR = 20.1, p = 0.01, 95% CI = 0.99 to 409.3). These haemorrhages developed at a median of 14 days. CONCLUSIONS: Submacular haemorrhages seem to be a significant adverse event following intravitreal bevacizumab in large occult choroidal neovascularisation and may affect visual outcomes. Prospective studies are required to establish the optimal dose of bevacizumab for larger lesion sizes or to identify the most appropriate anti-VEGF agent in large occult CNV with fibrovascular and serous PED lesions.

HLA and eye disease: a synopsis.

Human leukocyte antigen (HLA) gene products have been implicated in the pathogenesis of an increasing number of eye diseases, mainly inflammatory in nature. This perspective reviews the current hypotheses for why HLA polymorphisms are associated with specific eye diseases. Statistical problems in studies involving HLA associations are discussed, and possible solutions outlined. The relevance of HLA testing in routine ophthalmic practice, its practical and cost implications is also assessed.