ANTERIOR CHAMBER FLARE DURING BEVACIZUMAB TREATMENT IN EYES WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To study the anterior chamber flare during bevacizumab treatment of exudative age-related macular degeneration. METHODS: During a 2-year prospective follow-up, 50 patients recently diagnosed with exudative age-related macular degeneration were treated at once-a-month visits if subretinal or intraretinal fluid or a new hemorrhage was present in the lesion area. Flare was measured weekly during the first month and then monthly in both eyes. RESULTS: Higher flare was associated with older age (P = 0.007, Linear Mixed Model), higher number of smoking pack-years (P = 0.019), macular cysts (P = 0.041), and pseudophakia (P = 0.003). The levels gradually increased during the follow-up (P < 0.0001) but less in the eyes with classic CNV (P = 0.011). Flare decreased during treatment-free periods lasting for at least two consecutive visits (P = 0.005). A peak in flare was observed 1 week after the first injection (P = 0.034, Wilcoxon signed rank test). In the fellow eyes, higher flare values in the beginning of the follow-up were associated with later conversion into exudative age-related macular degeneration (P = 0.015, Mann-Whitney U test). CONCLUSION: Anterior chamber flare correlated poorly with the CNV activity. Higher levels may, however, precede or exist early in the process that leads to the development of exudative age-related macular degeneration.

Exudative age-related macular degeneration lesion components predicting microperimetric retinal sensitivity during anti-vascular endothelial growth factor treatment.

PURPOSE: To analyse the effect of exudative age-related macular degeneration (eAMD) lesion components on retinal sensitivity during anti-vascular endothelial growth factor treatment. METHODS: Visual acuity, fluorescein and indocyanine green (ICG) angiographies, autofluorescence images, microperimetries and optical coherence tomographies (OCTs) of 24 eyes of 24 patients were prospectively analysed in a 2-year study of pro-re-nata bevacizumab treatment for eAMD. Microperimetries were aligned with the OCTs, angiographies and autofluorescence images. Thicknesses of the neuroretina, pigment epithelial (RPE) elevation, neuroepithelial detachment (NED), subretinal tissue (SRT) and cystic intraretinal fluid were measured under each stimulus site, and areas of type 1 and type 2 macular neovascularizations (MNVs), ICG plaque, haemorrhage and RPE atrophy were identified. The effects and predictive values of lesion components on retinal sensitivity were analysed with multivariate mixed linear models for repeated measurements. RESULTS: The overall microperimetric retinal sensitivity increased during the first year (from 10.1 dB at baseline to 11.9 dB at 1 year; p = 0.021, Wilcoxon signed ranks), but remained the same during the second year (11.5 dB, p = 0.301). The baseline lesion components most strongly predicting deteriorated sensitivity at 1 year were RPE atrophy, the area of Type 2 MNV, intraretinal cysts, haemorrhage, Type 1 MNV and retinal thickening >350 µm. NED and RPE elevation had only small effects. At 2 years, the predictive values of the baseline lesion components remained quite unchanged. CONCLUSION: The most powerful predictors of retinal sensitivity loss during 2 years of treatment were RPE atrophy, areas of haemorrhage, the area of MNVs, intraretinal cysts and SRT. RPE elevation and NED had lesser effects.

Interleukin 8 promoter polymorphism predicts the initial response to bevacizumab treatment for exudative age-related macular degeneration.

PURPOSE: To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration. METHODS: Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months. RESULTS: Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain. CONCLUSION: The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Changes in anterior ocular structures and macula following deep sclerectomy with collagen implant.

PURPOSE: To determine the effect of intraocular pressure (IOP) lowering with deep sclerectomy (DS) on visual acuity, macular structures, and anterior ocular dimensions during the early postoperative period. METHODS: We prospectively analyzed 35 eyes of 35 patients scheduled for DS. Our focus with the measurements was on early postoperative changes in anterior ocular and macular structures related to IOP lowering during the first month after DS. In addition to a clinical ophthalmologic examination, our measurements included corneal topography, measurement of ocular dimensions with optical biometry, and examination of macular structure with optical coherence tomography. These measurements were repeated 1, 2, and 4 weeks postoperatively. RESULTS: Best-corrected visual acuity (BCVA) decreased 1 week postoperatively to 0.22 (0.20) LogMAR (p = 0.006). The BCVA then increased to its preoperative level, 0.17 (0.18) (p = 0.28), after 4 weeks. Axial length decreased from 24.12 (1.81) mm to 24.04 (1.81) (p<0.001) 4 weeks postoperatively. The steeper meridian of corneal curvature and average corneal power increased postoperatively; central corneal thickness was decreased. No significant change appeared in other measurements. CONCLUSIONS: We found changes in corneal curvature and ocular dimensions after DS. These changes were relatively small and do not completely explain the decrease in visual acuity postoperatively. Macular structures showed no changes.

The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

PURPOSE: To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. METHODS: Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. RESULTS: Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. CONCLUSION: Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.

Correlation between components of newly diagnosed exudative age-related macular degeneration lesion and focal retinal sensitivity.

PURPOSE: To analyse lesion components determining retinal sensitivity in microperimetry in eyes with newly diagnosed exudative age-related macular degeneration (AMD). METHODS: Visual acuity, contrast sensitivity, microperimetry, optical coherence tomography (OCT), and fluorescein (FA) and indocyanine green (ICGA) angiographies of 23 eyes of 23 patients were analysed. Central microperimetry grids with 28 test stimulus sites were automatically aligned with three-dimensional OCTs and manually aligned with angiographies. Thicknesses of the neuroretina, neuroepithelial detachment (NED), retinal pigment epithelial (RPE) elevation and subretinal tissue were measured under the 644 microperimetry stimulus sites. Areas of classic and occult choroidal neovascularizations (CNVs), subretinal and intraretinal haemorrhage, and late hyperfluorescence in ICGA were identified. The impact of the lesion components on retinal sensitivity was evaluated with correlation analysis and multivariate modelling. RESULTS: Decreased retinal sensitivity correlated significantly with the presence of CNV, haemorrhage, subretinal tissue and RPE elevation. Out of the OCT parameters, the most important determinant of sensitivity was the thickness of RPE elevation (Spearman's rho, r = -0.202, p < 0.0001). The thicknesses of subretinal tissue (r = -0.168, p < 0.0001) and NED had weaker effects (r = -0.147, p < 0.0001), and the neuroretinal thickness remained nonsignificant. In multivariate modelling, RPE elevation and subretinal tissue in OCT, CNV membranes in angiographies and haemorrhage had the strongest impacts on retinal sensitivity. CONCLUSION: The most important lesion components affecting retinal function were RPE elevation and subretinal tissue in OCT as well as neovascular membranes and haemorrhage in angiographies. NED and neuroretinal thickening remained less significant.