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.

Analysing Subgroups and Treatment Discontinuation in a Finnish Cohort of Patients with Neovascular AMD.

PURPOSE: We aimed to study the regional detailed visual outcome and treatment discontinuation of neovascular age-related macular degeneration (nAMD). METHODS: Clinical records of 110 patients treated for nAMD at the sole referral centre in the Helsinki region were analysed retrospectively. The follow-up was up to the fourth year. RESULTS: The mean visual acuity (VA) at baseline was 56.3 (SD 16.2) letters. The mean last VA at the first year was 59.7 (20.2), and the corresponding values for the second, third, and fourth years were 60.8 (20.6), 60.0 (19.0), and 59.7 (19.3). The mean difference from baseline was +3.39 (SD 14.6), +3.59 (17.6), +0.08 (18.9), and +3.08 (14.3). The number of patients declined each year, with only 51% of the patients being in treatment until the fourth year. The patients with shorter duration of follow-up tended to have a lower baseline VA, lesser gains, and an earlier decline in VA. The VA levels at the last visit were poorer in the shorter follow group. The initial VA response predicted later VA, whereas VA at baseline, age, or sex had no effect. However, the effect vanished with a longer time in treatment. CONCLUSIONS: Long-term VA stabilization was obtained in a regional material. Patients with neovascular AMD consist of cohorts with varying visual outcome and treatment time. Many of the patients benefit from the treatment for some time, however. When comparing real-world results, the outcome of the different follow-up time cohorts should be considered. This calls for new methods for analysing real-world nAMD treatment results.

Early middle age cholesterol levels and the association with age-related macular degeneration.

PURPOSE: To examine whether serum cholesterol in early middle age is associated with age-related macular degeneration (AMD) later in life. METHODS: A group of Helsinki Businessmen Study (HBS) participants (n = 209) were recruited for the study. Total cholesterol (TC), triglyceride and body mass index (BMI) were measured at the HBS baseline visit in 1964-1973. Lipid subfractions, BMI, smoking status and statin use were recorded in 2011 and fundus photographs graded for AMD in 2005-2012. The subjects were genotyped for the main AMD risk single nucleotide polymorphisms (SNPs). RESULTS: TC measured at baseline 1964-1973 was significantly higher in subjects later developing intermediate or late AMD (6.67 mmol/l versus 6.20 mmol/l, p = 0.024) or with drusen size of ≥125 µm (6.68 mmol/l versus 6.21 mmol/l, p = 0.030) compared with the rest of the study population. TC, LDL and TG values at follow-up 2011 were lower in subjects with AMD compared to those without, whereas HDL levels showed no difference. In multivariate analysis, baseline TC associated with intermediate or late AMD (OR 1.59, p = 0.004) and drusen size ≥ 125 µm (OR 1.57, p = 0.006) when corrected for age, BMI, AMD risk SNPs and smoking. Lipid values measured 2011 had no associations after correction. CONCLUSIONS: High systemic total cholesterol in early middle age may have a role in the initial development of AMD, especially in patients later developing large drusen.

Fluocinolone acetonide intravitreal implant (Retisert® ) in the treatment of sight threatening macular oedema of juvenile idiopathic arthritis-related uveitis.

PURPOSE: We describe eight patients with juvenile idiopathic arthritis-related chronic uveitis, who received a fluocinolone acetonide implant (FAI, Retisert®, Bausch&Lomb) in one eye. All patients had poor visual acuity (VA) due to persistent macular oedema in one or both eyes despite treatment with antirheumatic medication. METHODS: Median age of the patients was 22.9 years (range, 14.1-39.7) and duration of uveitis 13.0 years (range, 6.8-28.4) at FAI implantation. Median preoperative best-corrected visual acuity (BCVA) was 0.1 (range, 0.05-0.4) and Standardization of Uveitis Nomenclature, SUN-grade was SUN 2+ (range, 0.5-4.0). All patients had been treated extensively with systemic corticosteroids and antirheumatic drugs by the time of FAI implantation. The median follow-up time was 5.3 years (range, 4.4-6.3). RESULTS: Macular edema resolved in a median time of 0.2 years (range, 0.04-0.39) after the FAI implantation. The median BCVA was 0.5-0.63 (range, 0.1-1.0) from 1 to 5 years of follow-up. Macular edema did not recur in 5 eyes after the implantation. In three eyes, the macular oedema relapsed at 2.7, 2.9 and 5.5 years of follow-up. All our patients needed antirheumatic drugs in addition to the FAI to treat their macular edema. During the follow-up, 7 eyes required further intraocular operations: 4 cataract operations, 4 intraocular pressure -lowering operations and 1 retinal detachment surgery were performed. CONCLUSION: Fluocinolone acetonide implant is a valuable option in the treatment of persistent macular edema associated with JIA-related uveitis refractory to systemic treatments.

The Finnish national guideline for diagnosis, treatment and follow-up of patients with wet age-related macular degeneration.

Age-related macular degeneration (AMD) is the main cause of visual impairment in developed countries. Several improvements in the visualization of posterior segment of the eye together with the introduction of intravitreal anti-VEGF treatment have revolutionized the prognosis of the wet form of AMD (wAMD). Increasing incidence of wAMD together with the limited resources of society and of the healthcare system poses challenges for the provision and development of care. In context of these current aspects, we aimed to set evidence-based medical guidelines for diagnosis, treatment and follow-up of patients with wAMD.

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.

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.

Increased intravitreal angiopoietin-2 levels associated with rhegmatogenous retinal detachment.

PURPOSE: To explore factors related to pathogenesis of rhegmatogenous retinal detachment (RRD) and development of proliferative vitreoretinopathy (PVR), vitreous levels of angiopoietin-1 and -2 (Ang-1 and -2), previously undefined in RRD, transforming growth factor-(TGF) ß1, vascular endothelial growth factor (VEGF), erythropoietin (EPO) and proteolytic mediators of extracellular matrix remodelling (MMP-2 and -9) were compared in eyes with RRD and eyes with idiopathic macular hole or pucker. METHODS: Vitreous samples were collected from 117 eyes with RRD (study group) and 40 eyes with macular hole or pucker (control group). Growth factors were measured by ELISA and matrix metalloproteinases (MMPs) by gelatin zymography. RESULTS: The mean vitreous concentrations of Ang-2, MMP-2, and MMP-9 were higher (all p < 0.01), whereas concentration of VEGF was lower (p = 0.01) in eyes with RRD relative to controls. Logistic regression analysis identified Ang-2 concentration as a novel marker of RRD (p = 0.0001, OR 48.7). Ang-1, EPO, and total TGF-ß1 levels were not significantly different between the groups. However, TGF-ß1 and MMP-2 were increased in eyes with total RRD compared to those with local RRD (p ≤ 0.05). In eyes with PVR, no differences were observed in any studied marker as compared with non-PVR eyes. CONCLUSIONS: Current results reveal Ang-2 as a key factor upregulated in RRD. It may co-operate with fibrosis-associated factors and contribute to vascular complications such as breakdown of blood-eye barrier and PVR development.

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.

Leucocyte telomere length in age-related macular degeneration.

PURPOSE: To evaluate the association between telomere length and age-related macular degeneration (AMD). METHODS: Circulating leucocyte telomere length and the proportion of telomeres <5 kb were analysed in blood DNA samples taken from 121 patients with exudative AMD (83%), large drusen (14%) or central geographic atrophy (3%). Controls consisted of 77 age-matched subjects without AMD. The AMD status was assessed by a masked analysis of fundus photographs or angiographs. Telomere length was measured by Southern blotting. RESULTS: Mean (SD) telomere length was 7.76 kb (0.68) in AMD patients and 7.83 (0.69) in controls (p = 0.485). The corresponding proportions of telomeres <5 kb were 10.60 (2.76) and 10.05 (2.64) (p = 0.197). In this material, there was no correlation between telomere length and age, gender or smoking status. There were no differences between the major AMD risk single-nucleotide polymorphisms (SNPs) of the CFH, HTRA1 or C3 genes, expect for somewhat longer telomeres in controls with the C3 risk SNP. There were no differences in telomere length between patients with drusen or exudative AMD. CONCLUSIONS: Telomere length is not associated with exudative AMD or high-risk drusen.

Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFß1 in diabetic eyes undergoing vitrectomy.

PURPOSE: Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia-induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9), angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor-ß1 (totalTGFß1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker. METHODS: Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006-2008. Vitreous samples were collected before the start of the conventional 3-ppp vitrectomy. Vitreous MMP-2 and MMP-9, Ang-1 and Ang-2, VEGF, EPO and TGFß1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls. RESULTS: Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP-2 (p = 0.0015), totalMMP-2 (p = 0.0011), proMMP-9 (p = 0.00001), totalMMP-9 (p < 0.00001), Ang-2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFß1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang-2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9). CONCLUSION: The main new finding is that the intravitreal concentrations of Ang-2 correlated significantly with MMP-9, VEGF, EPO and TGFß1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.

Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis.

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind. Here, we show that in-transit tumor cells inside lymphatic vessels in mice bearing mouse melanomas or human lung tumors give rise to metastases. Using photodynamic therapy with the benzoporphyrin derivative verteporfin, we selectively destroyed lymphatic vessels in mice and pigs. Destruction of tumor-associated lymphatic vessels also eradicated intralymphatic tumor cells and prevented metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels. These findings highlight the potential of targeting in-transit tumor cells in patients.

Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration.

PURPOSE: To evaluate the role of vascular endothelial growth factor (VEGF) gene polymorphisms in exudative age-related macular degeneration (AMD). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Patients with recent exudative AMD (n = 162) and age-matched subjects without AMD (n = 85). METHODS: Fluorescein angiography (FA), clinical examination, and single nucleotide polymorphism (SNP) genotyping. MAIN OUTCOME MEASURES: The frequencies of 3 VEGF gene SNPs were analyzed, 1 at the promoter site (rs699947, A-->C) and 2 intronic SNPs (rs2146323, A-->C, and rs3025033, A-->G), in relation to the risk of AMD, to choroidal neovascular (CNV) lesion size and configuration, and to the anatomic response to photodynamic therapy (PDT). These SNPs were chosen to cover all the haploblocks of the VEGF gene. The 86 patients who had undergone PDT were classified as either PDT responders or PDT nonresponders based on the outcome of PDT after the last treatment session. For the PDT responders, the treating physician had deemed the lesion to be clinically dry and without leakage from CNV in FA at a visit scheduled at least 12 weeks after the last PDT treatment. For the PDT nonresponders, the PDT sessions had been discontinued by the treating retina specialist because of an apparently poor response and a still exudative lesion after several PDT sessions. RESULTS: The presence of exudative AMD or lesion size or configuration was not associated with the SNPs studied here. The frequencies of the rs699947 were significantly different in PDT nonresponders and PDT responders. The AA, AC, and CC genotypes were 14%, 39%, and 46%, respectively, in PDT nonresponders, compared with 40%, 48%, and 12%, respectively, in the PDT responders (P = 0.0008). The corresponding frequencies for the rs2146323 AA, AC, and CC genotypes were 4%, 32%, and 64%, respectively, in nonresponders and 24%, 38%, and 38%, respectively, in responders (P = 0.0369). The genotypes of the rs3025033 SNP were distributed evenly between the responders and nonresponders. CONCLUSIONS: The VEGF gene polymorphic SNPs at rs699947 and rs2146323 are strong determinants of the anatomic outcome after PDT, but the SNPs studied were not associated with the presence of exudative AMD or with the CNV lesion size or configuration. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

[Identification of susceptibility genes for age-related macular degeneration--a success story of molecular genetics]. / Silmänpohjan ikärappeuman alttiusgeenien tunnistaminen--molekyyligenetiikan menestystarina.

The number of persons over 70 years of age with advanced age-related macular degeneration in Finland can be estimated to be approximately 50,000. Milder forms are additionally present in a considerably larger group. Smoking and age are undisputed non-genetic risk factors of age-related macular degeneration. Of the genetic factors, polymorphisms of the complement factor H (CFH) and LOC387715 genes have a strong impact on the risk of developing the disease, whereas alleles of the C3, CFB, and the C1 inhibitor SERPING1 genes of the complement system exhibit only minor effects.

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

Primary intraocular lymphoma: improving the diagnostic procedure.

OBJECTIVE: To analyze the clinical features of primary intraocular lymphoma (PIOL) and to describe cytochemical and immunocytochemical findings of the vitreous specimens as well as the reasons for delayed diagnosis of PIOL. DESIGN: Prospective noncomparative study. PARTICIPANTS: Eleven patients referred to the uveitis or medical retina units, Department of Ophthalmology, University of Helsinki, were diagnosed as having PIOL between 2000 and 2005. The median follow-up of the patients was 32 months. METHODS: Clinical features and diagnostic workup of uveitis were described. Twelve vitrectomies were performed on 9 patients. The first 5 biopsies were fixed in an equal volume of 50% alcohol. The specimens of the next 7 vitrectomies were handled without alcohol, and tissue culture medium was added to the samples. MAIN OUTCOME MEASURES: Clinical features of PIOL, intervals from ocular symptoms and from first ophthalmological examination to diagnosis, and the role of a proper handling of the vitreous sample in the diagnosis of PIOL. RESULTS: Six females (54%) and 5 males (46%) (median age, 61 years) were included. Ten patients had ocular symptoms for 1 to 30 months (median, 8) before the first contact with an ophthalmologist. Uveitis was bilateral in 9 patients. Vitreitis was seen in all patients, and it was severe in 8. Fundus lesions dominated in 3 patients. Six patients lost useful vision in one eye before the diagnosis of PIOL. Cytologic and immunohistochemical stainings prepared of the unfixed vitreous specimens showed PIOL in 6 patients. The samples fixed in alcohol were nondiagnostic in 4 patients, and in them, verification of diagnosis was based on brain biopsy (3) or cerebrospinal fluid (1) findings. Seven patients died due to primary nervous system lymphoma. CONCLUSIONS: Diagnosis of PIOL is difficult but can be improved. Severe bilateral vitreitis in an elderly patient is a characteristic finding of PIOL. Alcohol fixation may jeopardize the identification of PIOL cells in the vitreous sample. Optimal handling of the vitreous specimens and examination of the slides by an experienced cytopathologist are critical in the diagnostic workup of PIOL.

Leucine 7-proline 7 polymorphism in the signal peptide of neuropeptide Y is not a risk factor for exudative age-related macular degeneration.

PURPOSE: Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, we set out to determine the presence of the leucine 7-proline 7 (Leu7Pro) polymorphism in exudative age-related macular degeneration (AMD) patients and to analyse its implications. METHODS: Genotype analysis of the Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY was performed in blood samples from exudative AMD patients (n = 240) and control subjects (n = 79). RESULTS: In all, 11% of exudative AMD patients and 14% of control subjects exhibited the NPY signal peptide Leu7Pro polymorphism. There were no statistically significant differences in Leu7Pro polymorphism frequency between the exudative AMD and control cases, as analysed by Fisher's exact two-sided test. CONCLUSIONS: Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY is not a risk factor for exudative AMD.

Transscleral red-laser cyclophotocoagulation combined with limited anterior retinal cryocoagulation in neovascular glaucoma.

PURPOSE: To evaluate transscleral contact red-laser cyclophotocoagulation (CPC), using a visible red 647-nm krypton or 670-nm diode laser and limited transscleral anterior retinal cryocoagulation in neovascular glaucoma. METHODS: In a retrospective case series, 35 eyes of 35 consecutive patients treated during a period of 6 years were included in the study. Inclusion was dependent on follow-up of at least 1 month. Patients who had undergone previous cyclodestructive procedures and patients who received an additional glaucoma operation in conjunction with CPC were excluded. In the combined procedure, the power per CPC application was 370-450 mW and exposure time was 10 seconds. One to two rows of cryoapplications were given to 360 degrees of the anterior retina. RESULTS: The success rate in terms of intraocular pressure (IOP of 8-21 mmHg or a decrease in IOP > 30%) was 89% at the last follow-up (17 +/- 15 months). Iris neovascularization regressed in 51% of eyes. Hypotonia developed in one (3%) eye (IOP of 5 mmHg). No cases of phthisis bulbi were seen. Visual acuity (VA) declined in 49% of eyes. CONCLUSIONS: A combination of transscleral contact red-laser CPC with limited anterior retinal cryocoagulation is efficient in lowering IOP in neovascular glaucoma and is well tolerated. During follow-up, a decrease in VA occurs in a significant proportion of patients.

Strontium plaque brachytherapy for exudative age-related macular degeneration: three-year results of a randomized study.

OBJECTIVE: To determine the efficacy of strontium plaque (Sr90) brachytherapy for age-related macular degeneration (AMD) with subfoveal choroidal neovascularization (CNV). DESIGN: Randomized clinical trial. PARTICIPANTS: Eighty-eight eyes of 86 patients with subfoveal CNV secondary to AMD were randomized either to plaque radiotherapy or to observation. INTERVENTION: Radiotherapy was given as episcleral brachytherapy using Sr90 plaques. Two different plaque types were used. Plaque I had a diameter of 8 mm and delivered a dose of 15 Gy at a depth of 1.75 mm in 54 minutes. With plaque II, the corresponding values were 4 mm, 12.6 Gy, and 11 minutes. The control group was observed without any treatment. MAIN OUTCOME MEASURES: The primary outcome measure was visual acuity at 6, 12, 24, and 36 months. Other outcome variables were contrast sensitivity, fluorescein angiographic, and clinically evaluated changes in the macula. RESULTS: Eighty-two patients (84 eyes [95%]) completed the 1-year follow-up, and 80 (93%) and 74 (86%) patients completed the 2- and 3-year follow-ups, respectively. At 6 months, visual loss of > or =3 lines occurred in 20% of treated patients and 42% of control patients (P = 0.031). At 12 months, a visual loss of > or =3 lines occurred in 45% (treated) and 56% (controls) (P = 0.325); at 24 months, in 73% and 71% (P = 0.914); and at 36 months, in 80% and 84% of patients (P = 0.591), respectively. Patients irradiated with plaque I had better results: a visual loss of > or =3 lines occurred in 6% at 6 months (P = 0.008, relative to controls), in 18% at 12 months (P = 0.007), in 59% at 24 months (P = 0.348), and in 71% at 36 months (P = 0.212). In patients treated with plaque II, the corresponding values were 29% (P = 0.032), 65% (P = 0.459), 83% (P = 0.317), and 80% (P = 0.687) at 6, 12, 24, and 36 months, respectively. CONCLUSIONS: The short-term clinical course of exudative AMD is affected by Sr90 brachytherapy, but by 12 months, there was no treatment benefit. This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha.