Photodynamic therapy in VEGF inhibition non-responders-Pharmacogenetic study in age-related macular degeneration assessed with swept-source optical coherence tomography.

BACKGROUND: Treatment of neovascular age-related macular degeneration (nAMD) remains a major challenge in ophthalmology. It is essential to determine which of VEGF inhibition non-responders can benefit from photodynamic therapy (PDT). As AMD is strongly related to gene polymorphisms, genetic factors can modify efficacy of treatment. Swept-source optical coherence tomography (SS-OCT) gives exceptional insight into the retina and choroid. SS-OCT usefulness needs to be evaluated in nAMD patients. METHODS: Prospective 6-month study included consecutive 110 patients (110 eyes) with predominantly classic neovascular AMD treated with photodynamic therapy. Only non-responders to anti-VEGF were included in the study. Greatest linear dimension (GLD) of the lesion, best corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and central choroidal thickness were assessed and compared between CFH and ARMS2 genotype groups. Success rate was the main endpoint. It was defined as not active CNV in the center of the fovea and no worsening in BCVA. Multiple regression was used to assess gene polymorphisms influence on PDT results. Wilcoxon tests were performed to determine significance of changes from baseline values. RESULTS: Following genotype frequencies were obtained-CFH CC 35 patients (31.8%), CT 52 (47.3%), TT 23 (20.9%); ARMS2 TT 28 patients (25.4%), GT 43 (39.1%), GG 39 (35.4%) success rate in CC/CT/TT CFH and TT/GT/GG ARMS2 groups were as follows respectively: 22.9%, 28.8%, 30.4% and 28.6%, 25.6%, 28.2%. The differences were not significant with highest odds ratio TT vs. CC CFH 1.57 (95% CI 0.48-5.2, p=0.4). Significant increase in GLD was observed only in CC CFH group. Overall mean following measured parameters were obtained at baseline/day 7/month 3/month 6 (significant changes from baseline are marked with asterisk): GLD-3825±1301µm/3901±1579µm/3861±1463µm/3925±1523µm; CSMT-405±203µm/434±257µm*/321±163µm*/295±157*µm; CCT-235±103µm/278±157*µm/211±113µm*/201±107*µm; BCVA-49.3±12.5/43.2±14.2*/49.6±11.6/48.7±12.2 letters on ETDRS charts. In all patients classic component of the lesion was assessed with SS-OCT with no need to be reaffirmed in FA. Thus FA was used mainly for lesion size calculation. CONCLUSIONS: Common genetic factors seem not to influence PDT effectiveness in VEGF inhibitors non-responders. SS-OCT is a valuable tool of nAMD monitoring, especially for choroid assessment. Deterioration of retinal structure and function is observed one week after PDT. It is related to increase in both retinal and choroidal thickness and is accompanied by mild temporary BCVA decrease.

Comparative Study of Anterior Eye Segment Measurements with Spectral Swept-Source and Time-Domain Optical Coherence Tomography in Eyes with Corneal Dystrophies.

PURPOSE: To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs). METHODS: Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots. RESULTS: Good agreement between the TD and SS OCT measurements was demonstrated for mCCT and aCCT in normal individuals and for mCCT in the CDs group. The ACD, nTIA, and tTIA measurements differed significantly in both groups. TBCD, LCD, and FECD caused increased CCT. MCD caused significant corneal thinning. FECD affected all analyzed parameters. CONCLUSIONS: Better agreement between SS OCT and TD OCT measurements was demonstrated in normal individuals compared to the CDs group. OCT provides comprehensive corneal deposits analysis and demonstrates the association of CD with CCT, ACD, and TIA measurements.

A69S and R38X ARMS2 and Y402H CFH gene polymorphisms as risk factors for neovascular age-related macular degeneration in Poland - a brief report.

BACKGROUND: The wet form of age-related macular degeneration (ARMD) is a leading cause of irreversible blindness in Caucasians. Our purpose was to assess influence of gene polymorphisms A69S (rs10490924) and R38X (rs2736911) ARMS2 and Y402 (rs1061170) CFH on wet ARMD risk in a Polish population. MATERIAL/METHODS: 130 unrelated patients (90 with wet ARMD and 40 controls) took part in the study. Dry blood was used for DNA isolation. PCR amplification and gene sequencing were performed. In subjects with R38X and A69S, SNP gene cloning was used to exclude the possible combined variant. RESULTS: Homozygous Y402H and A69S conferred a significance risk of wet ARMD in Poland: Y402H odds ratio (OR) was 5.57 (95% confidence interval: 1.58-19.6), p=0.002; and A69S OR was 7.72 (95% confidence interval: 1.73-34.36), p=0.001. R38X is probably more common in healthy subjects: OR was 0.45 (95% confidence interval: 0.19-1.05), p=0.053. CONCLUSIONS: The etiologic role in ARMD of A69S ARMS2 and Y402H CFH gene variants were confirmed in a Polish population for the first time. R38X variant of ARMS2 seems to be protective from wet ARMD.

Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration.

PURPOSE: To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. METHODS: This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 µm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance. RESULTS: Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 µm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746-0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA. CONCLUSIONS: Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved.

[Optical coherence tomography in diagnosing adult-onset vitelliform macular dystrophy]. / Zastosowanie optycznej tomografii koherentnej w rozpoznawaniu dystrofii zóttkowatej plamki doroslych.

PURPOSE: To assess usefulness of optical coherence tomography (OCT) in adult-onset vitelliform macular dystrophy (AVMD) diagnosis. To assess retinal pathological changes during all stages of the disease. MATERIAL AND METHODS: Retrospective case-series report. 16 patients (9 men, 7 women, mean age 60.25), with vitelliform macular dystrophy, who underwent ophthalmic examination including optical coherence tomography (OCT Stratus III, Zeiss Meditec, CA, USA) in 2005 and 2006. Retinal Thickness Map and Fast Retinal Thickness Map Acquisition Protocols were used during OCT scanning. Patients were evaluated with ETDRS charts, biomicroscopy, fluorescein angiography and electrophysiological exams. RESULTS: 7 patients (44%) were referred to our outpatient clinic with diagnosis of macular hole, 7 patients (44%) with diagnosis of AMD. In 2 patients Best disease was suspected. Diagnosis of AVMD was possible to establish in all patients including medical history, fundus photography and OCT. CONCLUSIONS: OCT enables retinal morphology assessment and can be treated as the basis of adult-onset vitelliform macular dystrophy early evaluation, diagnosis differentiation and monitoring progression.