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Inference from multiple markers is often encountered in biomedical research, especially when comparing treatments. Most common statistical methods rely on hypothesis testing with null hypothesis of no effect for each marker and methods based on closed testing for getting the combined p-value. This article proposes the use of simultaneous credible intervals obtained from the joint posterior distribution of effect measures of multiple markers for combined inference. The advantage of this method is that it finds the actual effect sizes and also allows different types of effect measures for various markers. We used equal tailed intervals and highest posterior density regions for effect measures of multiple markers. Simulation studies were carried out to examine frequentist properties of these simultaneous credible regions. These studies revealed that the inference based on simultaneous intervals can be different than the inference based on individual marker. The method is demonstrated through two case studies: (a) an observational study of wet age-related macular degeneration (wet-AMD); and (b) reanalysis of a randomized controlled trial for treatment of migraine. The wet-AMD observational study was the motivation for the present research.

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.

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 mu m (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 mu m (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.

Purpose We describe eight patients with juvenile idiopathic arthritis-related chronic uveitis, who received a fluocinolone acetonide implant (FAI, Retisert (R), 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. MethodsResultsMedian age of the patients was 22.9years (range, 14.1-39.7) and duration of uveitis 13.0years (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 5.3years (range, 4.4-6.3). Macular edema resolved in a median time of 0.2years (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 5years 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. ConclusionFluocinolone acetonide implant is a valuable option in the treatment of persistent macular edema associated with JIA-related uveitis refractory to systemic treatments.

PURPOSE To examine the clinical outcomes of intraocular lens (IOL) scleral fixation with the friction knot technique. METHODS Retrospective case series of 152 eyes of 152 patients with inadequate capsular bag support operated with the friction knot IOL scleral fixation technique by a single surgeon. The fixated IOLs were one-piece or three-piece models all with open loop haptics. Main outcome measures were change in corrected distance visual acuity (CDVA) and postoperative complications. RESULTS The mean follow-up time was 11.7 months (median 4.9, range 0.7-64.8). The mean logarithm of the minimum angle of resolution CDVA improved from preoperative 0.77 ± 0.73 (Snellen 20/118 ± 7.3 lines) to 0.44 ± 0.56 (Snellen 20/55 ± 5.6 lines) at the final visit (p

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.

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) β1, 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.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.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-β1 levels were not significantly different between the groups. However, TGF-β1 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.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.

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.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.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 (P0.001) correlated with less visual acuity gain.The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Although >20 common frequency age-related macular degeneration (AMD) alleles have been discovered with genome-wide association studies, substantial disease heritability remains unexplained. In this study we sought to identify additional variants, both common and rare, that have an association with advanced AMD. We genotyped 4,332 cases and 25,268 controls of European ancestry from three different populations using the Illumina Infinium HumanExome BeadChip. We performed meta-analyses to identify associations with common variants and performed single variant and gene-based burden tests to identify associations with rare variants. Two protective, low frequency, non-synonymous variants A307V in PELI3 (odds ratio [OR]=0.14, P=4.3×10−10) and N1050Y in CFH (OR=0.76, Pconditional=1.6×10−11) were significantly associated with a decrease in risk of AMD. Additionally, we identified an enrichment of protective alleles in PELI3 using a burden test (OR=0.14). The new variants have a large effect size, similar to rare mutations we reported previously in a targeted sequencing study, which remain significant in this analysis: CFH R1210C (OR=18.82, P=3.5×10−07), C3 K155Q (OR=3.27, P=1.5×10−10), and C9 P167S (OR=2.04, P=2.8×10−07). We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8x10−07; Firth corrected OR = 0.64, P = 9.6x10−11). This study supports the involvement of both common and low frequency protective variants in AMD. It also may expand the role of the high-density lipoprotein pathway and branches of the innate immune pathway, outside that of the complement system, in the etiology of AMD.

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.

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-β1 (totalTGFβ1) 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 TGFβ1 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 totalTGFβ1 (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 TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.

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

Purpose: To evaluate the association between telomere length and age-related macular degeneration (AMD). Methods: Circulating leucocyte telomere length and the proportion of telomeres

Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid, and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk factor for age-related macular degeneration (AMD). We, therefore, examined associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were diagnosed by fundus photographs and fluorescein angiography. The control group (no signs of AMD in fundus photographs) consisted of 55 men and 111 women. Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly associated (p = 0.0471) with AMD status when using a permutation procedure that controlled for the number of tested genotypes and genetic models. Odds ratio (OR) for the association was 1.699 (95% CI 1.192–2.423). The SNP consists of C/T alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%. Distribution of proportion of cases/controls between alleles revealed an additive genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel candidate for AMD genetic risk factor in Finnish population.

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.

Plasmin concentration was determined in tear fluid from 76 eyes showing corneal epithelial disorders, such as corneal ulcers and erosions due to trauma or contact lens wear. Nearly 70% of the eyes with corneal disease had plasmin in their tear fluid, whereas plasmin was present in only 20% of the eyes in a control group of 50 eyes. Re-examination of the plasmin positive control eyes revealed conjunctival bacterial growth or mild subclinical viral infection in most cases. We conclude that plasmin is released into the tear fluid in the presence of corneal or conjunctival lesions or infections, suggesting a pathogenic role of plasmin in these disorders. The significance of the occurrence of plasmin in tear fluid during corneal wound healing is discussed.

Transcleral contact retinal krypton laser photocoagulation of the retina was studied in rabbit eyes. The laser application was performed under indirect ophthalmoscope visual control with indentation of the sclera by the laser probe. Retinal lesions were produced with powers ranging from 0.2 to 0.3 W and application times between 1 and 2 sec. The lesions were studied histologically 2, 5, 10, 12, 20, 30 and 70 days after treatment. Histopathological examination of the lesions showed damage of mainly the outer retinal layers in light lesions, and to all layers of the retina in the more intense lesions. No scleral damage was observed in the light lesions, whereas transient oedema of the inner sclera was seen in the intense lesions. Studies with enucleated rabbit eyes showed that indentation of the sclera by the laser probe substantially decreased the power needed to produce a retinal lesion. It is concluded, that when used with scleral indentation, transscleral krypton laser photocoagulation of the retina can be performed with minimal damage to the sclera.

A computerized system for the localization of diabetic lesions from fundus photographs is described. The coordinates for each lesion in relation to reference points are determined from fundus images projected on a digitizing table. The program accepts some variation in coordinates for a single lesion, still to be recorded as the same lesion in a series of photographs, and the magnitude of this variation is adjustable. The data obtained from the localization program are transferred to a register program yielding the following parameters: number of lesions, new lesions, lost lesions, variable lesions, time of presence for lost lesions. These data can be further exported into Microsoft Excel 4, for analysis of large patient materials. An intra-observer error of 0% and an inter-observer error of 1.1% was found in localization of lesions from fundus images. The program was insensitive to small variations in the fundus pictures, but comparisons of 30 degrees and 60 degrees photographs of the same fundus, or 20 degrees deviation of gaze, induced identification errors in 2.9% and 11.9% of localizations, respectively. With this system new parameters on diabetic fundus images can be obtained. The significance of these parameters in the progression of diabetic retinopathy will be analyzed in further studies.

This report examines the changes that occurred in the post-operative visual and social function of patients with cataract when the hospital responsible for cataract treatment (roughly 1000 cataract extractions per year) shifted from non-IOL to IOL techniques. Visual function and vision-dependent social performance were compared retrospectively in 116 patients, 53 of whom had undergone cataract extraction without IOL implantation, and 63 of whom had been treated by IOL implantation. Patients with no IOL had the possibility of using extended-wear contact lenses if unable to tolerate aphakic spectacles. Visual results and social rehabilitation were good with both techniques, and there was no significant difference in vision-dependent social performance between the groups. The quality of vision and patient satisfaction with surgery were better in IOL patients. It appears that, once vision is restored by surgery and contact lenses are available, post-operative function in patients is determined by factors other than the type of cataract surgery. However, the shift to IOL surgery brings about improved quality of vision and patient satisfaction.

Nineteen patients with malignant uveal melanomas were treated with I-125 applicators. There were 10 males and 9 females with a median age of 61 years (range 42-76). The tumour was located in the choroid in 12 eyes and in the choroid and ciliary body in 7 eyes. The size of the tumours was 7-18 mm in maximal basal diameter (median 12), 5-16 mm in minimal basal diameter (median 10), and 5.5-15 mm in thickness (median 8.5). The volume of the tumours was 123-1890 mm3 (median 540). All tumours were classified as large (T3). For the irradiation, a computer program, which calculates three-dimensional dose distribution of I-125 seeds in gold plaques, was developed. By modifying the seed positions, activity and the orientation, patients can be treated individually. Iodine-125 emits low energy photons, ideal for intraocular tumour therapy and tissue. Extra-ocular tissue located behind the applicator can be completely shielded by a 0.5 mm gold layer. The dose at the apex of the tumour ranged from 30 to 120 Gy (median 93). The treatment time ranged from 44 to 600 h (median 235). Preliminary results are good. After a median follow-up of 6 months, the tumour growth has been arrested in all eyes and in 10 eyes the tumour has decreased in size.

Purpose: To retrospectively evaluate the results of cyclophotocoagulation (CPC) with the transscleral contact red 670-nm diode laser in treating glaucoma. Methods: Cyclophotocoagulation was performed in 60 eyes of 60 patients with a mean age of 74 ± 11 years (range 49–90 years). The treatment was delivered via a fibre-optic probe. The power per application was 430 mW. Exposure time was 10 seconds. Results: The mean overall follow-up time after the initial CPC was 26 ± 20 months (range 3–75 months). Preoperative intraocular pressure (IOP) was 27 ± 11 mmHg (n = 60). After one or more CPC treatments, mean IOP decreased to 20 ± 7 mmHg (n = 51) at 1 month, 19 ± 5 mmHg (n = 45) at 3 months, 18 ± 5 mmHg (n = 29) at 6 months, 19 ± 7 mmHg (n = 22) at 1 year, 18 ± 7 mmHg (n = 16) at 2 years, 14 ± 4 mmHg (n = 8) at 3 years, and 18 ± 6 mmHg (n = 60) at the last follow-up. An IOP of 8–21 mmHg or a > 30% decrease in IOP was obtained in 33 of 41 eyes (80%) with baseline IOP > 21 mmHg at the last follow-up. Hypotonia (IOP

Purpose Photodynamic therapy (PDT) has been widely used in the treatment of age-related macular degeneration (AMD). The complement cascade has an important role in the tissue reactions occurring after PDT. The Y402H polymorphism of the complement factor H (CFH) gene has been identified as a risk factor for AMD. Since CFH is central in the regulation of the complement system the authors wanted to analyze whether the CFH Y402H polymorphism modifies the PDT outcome in AMD. Methods A total of 88 patients having been treated with PDT and without further scheduled PDT sessions were analyzed. Depending on the situation at their final PDT session the patients were classified retrospectively as PDT-responders or PDT-nonresponders. All patients were genotyped for the CFH Y402H polymorphism. Results The proportion of PDT-responders was 18/26 (69.2%) in patients homozygous for the CFH Y402H risk allele, 34/50 (68.0%) in heterozygous, and 7/12 (58.3%) in patients with the normal genotype (p=0.520). The median number of PDT treatments of the PDT-responders was three for all the genotypes. Conclusions The dysfunction of the CFH related to the risk of AMD and caused by the Y402H polymorphism does not modify the outcome of PDT. Genotyping for CFH Y402H cannot be used to select patients for this treatment.

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.

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.

Purpose: To evaluate the role of various vasoactive hormones in the evolution of diabetic retinopathy during pregnancy and postpartum. Methods: Retinopathy was graded from fundus photographs of 45pregnant women with type 1 diabetes and seven pregnant women without diabetes in a prospective study. Markers of renin-angiotensin-system (RAS), plasma renin activity (PRA), angiotensin II (AngII), aldosterone, natriuretic peptides (ANP, BNP, CNP) and adreonomedullin (AM) were measured during the first and third trimesters and at 3 months postpartum. The women with diabetes were grouped by progression of retinopathy during pregnancy and postpartum. Results: Levels of PRA (p ¼ 0.001) and ANP (p ¼ 0.03) were significantly lower in diabetes than in non-diabetes subjects throughout pregnancy and postpartum. No significant differences appeared in levels of AngII, aldosterone, AM, BNP or CNP between the two groups. In multivariate logistic regression analyses with retinopathy progression by the third trimester as the dependent variable, only duration of diabetes qualified in the model (p ¼ 0.027, R ¼ 0.227, Exp(B) ¼ 1.28). Conclusions: Diabetic pregnancy is associated with lower levels of PRA and ANP compared to non-diabetic pregnancy. Lowered RAS activity may contribute to the hyperdynamic blood flow and progression of DR during diabetic pregnancy. Within the power of this study no clear associations between the vasoactive hormones and progression of retinopathy could be detected.

The relation of maternal cytokine levels to retinopathy progression during diabetic pregnancy is a less studied subject. Therefore, we investigated levels of systemic proinflammatory markers, C-reactive peptide (CRP), interleukin-6 (IL-6) and circulating vascular cell adhesion molecule-1 (VCAM-1) during pregnancy and postpartum in relation to the progression of diabetic retinopathy (DR).A prospective follow-up study of 39 pregnant women with Type I diabetes and eight nondiabetic pregnant women was performed. DR was graded from fundus photographs. Plasma levels of systemic proinflammatory markers were measured by immunofluorometric assay (CRP) and by enzyme-linked immunosorbent assay (IL-6 and VCAM-1) in the first, second (diabetics only), third trimester of pregnancy, and 3 and 6 months postpartum (diabetics only).Our diabetic women had good glycaemic control (HbA1c 6.9 +/- 0.8). The levels of IL-6, VCAM-1, and CRP did not differ between diabetic and nondiabetic women throughout pregnancy and postpartum (repeated measures ANOVA between the groups). An association between CRP and progression of retinopathy was observed in diabetic women (P = 0.037). Additional evidence of inter-relationship could be revealed as CRP was higher in those diabetic women with worse glycaemic control (HbA1c) (P = 0.038).During pregnancy and postpartum, levels of proinflammatory factors (IL-6, CRP, VCAM-1) seem to be generally similar in Type I diabetic women compared to nondiabetic controls. However, CRP levels were higher in those diabetic women with progression of retinopathy and in those with worse glycaemic control.

Aims To evaluate the role of systemic angiopoietic factors in the progression of diabetic retinopathy during pregnancy. Methods In a prospective study of 26 pregnant women with diabetes and eight non-diabetic pregnant women, retinopathy was graded from fundus photographs. Plasma levels of angiopoietin-1, angiopoietin-2, human vascular endothelial growth factor A (hVEGF-A), and total soluble receptor of vascular endothelial growth factor (sVEGF) receptor-1 were measured during the first and third trimester and 3 months postpartum. Results In diabetic women, levels of angiopoietin-2 were 26.5 ng/ml (12.1–47.7) (median and range) during the first trimester, 2.9 ng/ml (0.6–3.5) during the third trimester, and 0.5 ng/ml (0.3–0.7) 3 months postpartum, compared with 44.3 (38.3–61.9), 5.7 (3.1–8.4) and 0.9 (0.6–4.9) ng/ml, respectively, in non-diabetic women (P = 0.002 between groups). Levels of angiopoietin-1 and sVEGF receptor-1 did not differ between the groups. Postpartum hVEGF-A levels were lowest in women with progression of retinopathy. In logistic regression analyses, progression of retinopathy during pregnancy was not explained by the levels of the angiopoietic factors. Conclusions The circulating levels of angiopoietic factors in pregnant diabetic women were either lower than (Ang-2) or similar to (Ang-1, hVEGF-A, VEGFR-1) those levels observed in non-diabetic pregnant women. The levels of angiopoietic factors measured here appear not to be connected with the progression of retinopathy during pregnancy.

Purpose: To report a case of delayed fungal endophthalmitis by Paecilomyces variotii following uncomplicated cataract surgery. To our knowledge this is the first reported case of postoperative endophthalmitis by this species. Methods: We report the longterm clinical follow-up of an 83-year-old female who underwent uncomplicated sutureless, small-incision cataract surgery. She developed recurring uveitis 4 months after surgery. Vitreous tap and finally complete vitrectomy with removal of the capsular bag including the intraocular lens were performed. Fungi were studied by histopathology and culture. Results: At histopathological examination, the fungi were found to be closely related with the capsular bag. A few mononuclear inflammatory cells were encountered. At culture, Paecilomyces variotii, a common ubiquitous non-pathogenic saprophyte, was identified. Despite systemic, intravitreal and topical antifungal therapy after vitrectomy the uveitis recurred several times, but no fungal organisms were isolated from the repeat intraocular specimen. At 18 months postoperatively the subject's visual acuity was finger counting at 2 metres. At the time of surgery the operating room air-conditioning system was undergoing repairs. Cases of fungal endophthalmitis after contamination from air-conditioning ventilation systems have been reported before, but none of the cases reported have been caused by P. variotii. Conclusion: P. variotii, a non-pathogenic environmental saprophyte, may be disastrous if introduced into the eye. International recommendations on the environmental control of the operating room air-conditioning ventilation system should be strictly followed. No intraoperative surgery should be undertaken while the air-conditioning system is undergoing repairs or service.

To study macular topography and contrast sensitivity (CS) in diabetic and nondiabetic women during pregnancy and post partum.A prospective study of 46 pregnant women with insulin-dependent diabetes and 11 nondiabetic pregnant controls. Macular surface topography was analyzed by Heidelberg Retinal Tomograph. Volume above the reference plane (VARP) was measured with 1.0-, 1.5-, 2.0-, and 3.0-mm-diameter circles. CS was measured with the Vistech 6500 Contrast Test System.The diabetic women had greater VARP than the controls measured with the 1.5-mm diameter circle. In diabetic women, the mean VARP was 0.084+/-0.064 mm(3) (mean +/- SD) in the first trimester, 0.080 +/- 0.056 mm(3) in the third trimester, and 0.087 +/- 0.067 mm(3) 3 months post partum compared with the values of 0.069+/-0.043, 0.054+/-0.024, and 0.036+/-0.020 mm(3) in the controls ( P=0.036 between groups). In diabetic women requiring laser treatment, the difference from controls was more significant ( P0.001). CS at 3 cpd and 6.0 cpd was lower in diabetic women than in controls throughout pregnancy and post partum ( P=0.012 and P=0.043). A statistically significant negative correlation appeared between macular topography and CS during the third trimester; between cpd 6 and VARP 1.5 mm ( r=-0.471, P=0.001), and between cpd 6 and VARP 2.0 mm ( r=-0.446, P=0.002).In the diabetic women, especially in those with clear progression of retinopathy during pregnancy and post-partum, the macula seemed to be slightly more elevated than in the controls, and CS was lower at mid-range spatial frequencies. CS loss in the diabetic women correlated with macular elevation during the third trimester.

OBJECTIVE— To evaluate the progression of retinopathy during pregnancy and postpartum in (insulin-dependent) women with type 1 diabetes treated with insulin lispro or with regular human insulin. RESEARCH DESIGN AND METHODS— A prospective open study of 69 pregnant women with diabetes was performed. A total of 36 of the women were treated with insulin lispro (lispro group) and 33 were treated with conventional short-acting human insulin (regular insulin group). The retinopathy level was estimated by color fundus photography every trimester and postpartum. Glycemic control during pregnancy, hypoglycemia (blood glucose level RESULTS— HbA1c values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy (P = 0.022, repeated-measures ANOVA). The number of hypoglycemic episodes did not differ between the treatment groups. In multivariable logistic regression analysis with retinopathy severity (Diabetes Control and Complications Trial level) in the third trimester as the dependent variable, only nulliparity qualified as a predictor in the model [Exp(B) = 4.0, 95% CI 1.1–13.7, P = 0.030]. Factors such as duration of diabetes, type of insulin used, mean HbA1c level throughout pregnancy, blood pressure (systolic or diastolic), preeclampsia in the current pregnancy, smoking, or prepregnancy planning did not explain the retinopathy progression. CONCLUSIONS— Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy.

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 AT, CFH rs1061170 TC, ARMS2 rs10490924 GT and C3 rs2230199 CG 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

Purpose. To study macular capillary blood flow velocity in diabetic and healthy women during pregnancy and the postpartum period. Methods. A prospective study of 46 pregnant women with insulin-dependent diabetes and 11 healthy pregnant women was performed. Macular capillary blood flow velocity was measured by blue-field entoptic simulation. Diabetic retinopathy was graded from colour fundus photographs. Results. In diabetic women, the macular capillary blood flow velocity was 0.94±0.27 mm/s (mean ± SD) during the first trimester, 1.00±0.28 mm/s during the third trimester and 1.03±0.24 mm/s 3 months postpartum, compared with values of 0.71±0.20, 0.77±±0.20 and 0.82±0.19 mm/s, respectively, in healthy women (P=0.0026 between groups). Diabetic women with no or very mild retinopathy had lower macular capillary blood flow velocities than those with more severe retinopathy (P=0.0164), but higher velocities than healthy women (P=0.0167). An increase temporally from the first trimester to the postpartum period was observed in diabetic women (P=0.0294) but not in healthy (P=0.2449) women. Conclusions. According to our study macular capillary blood flow velocity is higher in diabetic than in healthy women during pregnancy and the postpartum period. Further, capillary blood flow velocity seems to depend on the grade of retinopathy in pregnant diabetic women. These data support the concept that capillary hyperperfusion may play a role in the development of diabetic retinopathy during pregnancy.

PURPOSE To examine the effect of 670-nm diode laser cyclophotocoagulation on corneal morphology, density of corneal subbasal nerves, corneal mechanical sensitivity, and the rate of tear fluid secretion in human eyes. PATIENTS AND METHODS Transscleral contact cyclophotocoagulation was performed in 10 eyes of 10 consecutive patients on 180 degrees of the pars plicata of the ciliary body, using a 670-nm diode laser (power = 430 mW, application time = 10 seconds). In vivo confocal microscopy, with special attention to corneal morphology and the density of the subbasal nerves in the central and inferior perilimbal cornea, was performed preoperatively, and at 3 days and 1 month postoperatively. Corneal mechanical sensitivity was tested preoperatively, and at 3 days and 1 month postoperatively, using a Cochet-Bonnet esthesiometer. The rate of tear fluid secretion was measured preoperatively and 1 month postoperatively, using the Schirmer basic secretion tear test with topical anesthesia. RESULTS After cyclophotocoagulation, in vivo confocal microscopy did not reveal any changes in any of the corneal layers or in the corneal subbasal nerves. After treatment, as compared with baseline (paired samples test, > 0.05), there was no statistically significant change in the mechanical sensitivity values in any part of the cornea or in the Schirmer basic secretion tear test result. CONCLUSION The results of this preliminary study suggest that cyclophotocoagulation with the 670-nm diode laser does not impair corneal innervation.

In glaucoma, aqueous outflow into the Schlemm’s canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

This study investigated whether retinal capillary circulation in the macula is affected in exfoliation glaucoma and whether such changes can be detected in exfoliation syndrome without glaucoma. Blue-field entoptic simulation (measurement of macular capillary leukocyte velocity and density) was performed in 2 groups: 10 subjects with unilateral exfoliation glaucoma and 11 subjects with unilateral normotensive exfoliation syndrome. Macular capillary leukocyte velocity was reduced in exfoliation glaucoma but not in normotensive exfoliation syndrome.

Purpose To evaluate the usefulness of the krypton laser for transscleral contact cyclophotocoagulation (CPC) in the treatment of glaucoma in young patients. Design Retrospective noncomparative interventional case series. Participants Transscleral contact krypton laser CPC was performed in 27 glaucomatous eyes of 22 young patients (mean age, 10.5 ± 5.6 years; range, 11 months–19.4 years). Methods The treatment was delivered by means of a fiberoptic probe with compression of the sclera by the probe. The power used was 300 to 500 W per application at the tip of the probe with an exposure time of 10 seconds. Main outcome measures The primary outcome measure is a change in intraocular pressure (IOP). Results Of the patients who received CPC in both eyes, one eye was randomly chosen for statistical analysis. The mean overall follow-up time was 43.3 ± 25.3 (median, 36.5; range, 1–82) months after the initial CPC. Preoperatively, the mean intraocular pressure was 35.0 ± 7.9 mmHg (n = 22). After one or more CPCs, the mean IOP was decreased to 21.5 ± 8.7 mmHg (n = 22) at 1 month ( P P P P P Conclusions Krypton laser CPC is a well-tolerated means of lowering IOP in young patients with glaucoma, but repeated treatments may be needed.

PURPOSE: To evaluate the usefulness of the krypton laser for transscleral contact cyclophotocoagulation in the treatment of posttraumatic glaucoma. PATIENTS AND METHODS: A total of 18 eyes of 18 patients with therapy-resistant posttraumatic glaucoma treated with krypton laser cyclophotocoagulation from 1991 to 1996 were included in this review. The krypton laser was delivered by a fiberoptic probe with simultaneous compression of the sclera. The energy used was 3 to 5 J per application at the tip of the probe, with an exposure time of 10 seconds. The treatment covered 90 to 360 degrees of the ciliary body with approximately 10 applications per quadrant. RESULTS: With one or more cyclophotocoagulation treatments, the intraocular pressure decreased from the baseline mean (+/- standard deviation) of 32.6 +/- 12.8 mm Hg to 23.6 +/- 10.3 mm Hg (n = 17) at 1 month, to 21.8 +/- 7.5 mm Hg (n = 13) at 3 months, to 22.5 +/- 7.6 mm Hg (n = 13) at 6 months, and to 19.6 +/- 10.5 mm Hg (n = 18) at the last control visit (mean, 19.4 months; range, 3 weeks to 73 months) after cyclophotocoagulation but no other glaucoma procedure. At baseline, 17 (94%) of 18 patients were taking glaucoma medication, as were 15 (83%) of 18 patients at the last control visit. One (6%) case of phthisis occurred. CONCLUSIONS: Krypton laser cyclophotocoagulation is an effective and reasonably well tolerated means of lowering intraocular pressure in posttraumatic glaucoma. Because of the refractory nature of the disease, repeated treatments may be needed.

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.

PURPOSE To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. METHODS Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. RESULTS At 12 months visual acuity had improved or remained the same in 9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. CONCLUSIONS Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM.

AIM—To evaluate the correlation between the central visual field and changes in fluorescein angiography and fundus photography in patients treated with strontium plaque radiotherapy for subfoveal exudative age related macular degeneration (AMD). METHODS—Octopus program 34 automated static perimetry, fluorescein angiography, and colour fundus photography were performed on 19 patients at baseline and at 12 months after strontium-90 plaque therapy. A schematic picture outlining the areas of hyperfluorescent neovascular membranes and subretinal blood was drawn of a projected 30° fundus fluorescein angiogram. This drawing was superimposed on the size adjusted Octopus visual field. The changes in retinal sensitivity were calculated and related to angiographic changes. RESULTS—Three of the 19 patients had a reliability factor (RF) >15% and were excluded from further analysis. In the remaining 16 patients the mean defect (MD) and loss variance (LV) values remained unchanged in patients showing regression of the choroidal neovascular membrane (CNVM) to irradiation at 12 months. MD was 7.7 (SD 1.7) at baseline and 7.6 (1.9) at 12 months (p = 0.86), and LV was 32.6 (13.9) at baseline and 32.4 (15.7) at 12 months (p = 0.94). However, in patients with progression of the CNVM at 12 months, both the MD and LV increased significantly during the 12 month follow up (MD from 7.3 (2.9) to 13.1 (3.6) ( p = 0.05) and LV from 31.0 (22.9) to 71.8 (24.1) (p = 0.017)). When comparing the mean retinal sensitivity in the area of the primary CNVM (including classic, occult, and haemorrhagic components), the results were analogous: in patients with a regression of the CNVM after irradiation the mean sensitivity remained almost unchanged. It was 10.3 (6.4) dB at baseline and 9.4 (7.3) dB at 12 months (p = 0.58). In five out of 11 patients (45%) with regression of the CNVM, the mean retinal sensitivity even improved by 2.0-5.0 dB in the area of the original lesion during follow up. Instead, in patients showing progression of the CNVM at 12 months, there was a significant loss in mean retinal sensitivity—from 9.9 (4.6) dB at baseline to 1.0 (1.1) dB at 12 months (p = 0.019). The mean retinal sensitivity in the area of the irradiated but clinically normal retina during follow up was not significantly altered (21.5 dB at baseline, 19.7 dB at 12 months (p = 0.10)). CONCLUSIONS—Regression of subfoveal choroidal membranes in AMD after focal strontium irradiation is connected with stabilisation or even improvement of retinal sensitivity in central visual field measured by automated perimetry. Strontium plaque irradiation does not change the sensitivity in clinically normal paramacular retina during a 12 month follow up. Keywords: choroidal neovascular membranes; age related macular degeneration; Octopus perimetry; strontium

• Purpose: To study microaneurysm (MA) formation and disappearance rates during pregnancy and postpartum in diabetic women with mild diabetic retinopathy. • Methods: Red-free photographs were taken at the 12th, 24th and 32nd–36th weeks of pregnancy and 3 and 6 months postpartum from 21 type 1 diabelics with mild diabetic retinopathy. In a subset of 13 patients follow-up was continued until 1 year after pregnancy. Fundus photographs were analysed using a computer-assisted fundus lesion localization system. • Results: In the whole material the total MA count was 3.1 ±3.6 (mean±SD) at the 12th week, 3.4 ± 3.1 at the 24th week, 4.1±4.9 at the 32nd–36th week, 5.4±6.2 at 3 months postpartum and 5.2±5.8 at 6 motiths postpartum. We found that MA count increased during pregnancy, but it was highest 3 months postpartum. Both the rate of MA formation and the rate of MA disappearance increased during pregnancy, with the disappearance rate exceeding the formation rate 6 months postpartum, In patients having mean HbAlc levels below the median value of 6.38 mmol/1 there was a flare-up of MAs during pregnancy, levelling by 3 months postpartum. Patients with a higher than the median (0.76 mmol/1) decrease in HbAlc level compared to pre-pregnancy HbAlc also developed more MAs during the course of pregnancy. • Conclusions: These data suggest that there is continuons turnover of MAs during pregnancy. MA count increases during pregnancy but the MA coutil was highest 3 months postpartum, after which the formation rate started to decline. Temporary aggravation of mild retinopathy occurs in diabetic patients after normalization of blood glucose levels.

PURPOSE To analyze the appearance and disappearance of microaneurysms in different phases of fluorescein angiography. METHODS Three fluorescein angiograms were taken at 13-month intervals during a 26-month follow-up period from 13 patients with type I diabetes and mild background retinopathy. Two frames of the angiogram were analyzed: one from the transit phase and the other from the late phase of the angiogram. Individual microaneurysms were identified and localized from each frame using a computerized system for retrieval of the coordinates for each microaneurysm. Microaneurysms identified by their location then were analyzed in relation to the phase of the angiogram in which they were visualized and their disappearance during follow-up study. RESULTS Thirty-three percent of the microaneurysms were visualized only in the early phase, 31% in only the late phase, and 36% in both phases of the fluorescein angiogram. The microaneurysms frequently changed their phase of appearance in the angiogram during follow-up study. CONCLUSION During the 26-month follow-up period, between 55% and 80% of the microaneurysms present at baseline disappeared. The phase of the baseline angiogram in which the microaneurysms were visualized did not determine their disappearance rate.

Purpose To study the effects of IL-8, VEGF, CFH, complement component C3 and LOC387715 single nucleotide polymorphisms and neovascular lesion characteristics on the response to intravitreal bevacizumab treatment in exudative age-related macular degeneration (AMD). Methods Fifty patients with treatment naive exudative AMD were recruited to this two-year prospective follow-up study, and treated with bevacizumab on their once-a-month visits when sub- or intraretinal fluid in OCTs, or a new hemorrhage was detected. Visual acuities (VA) and contrast sensitivities (CS) were assessed on every visit, and fluorescein (FA) and indocyanine green (ICGA) angiographies recorded at baseline, and after one and two years of follow-up. Blood samples were collected for genotyping. Results VEGF -2578A/C and CFH Y402H polymorphisms and baseline lesion size in ICGA associated with the number of needed reinjections during the follow-up, and IL-8 -251A/T associated with the disappearance of fluid in OCTs. The alleles A in IL-8 -251A/T, A in VEGF -2578A/C, and C in CFH Y402H had a cumulative effect on the presence of fluid in OCTs. A marked difference existed between patients having 0 - 2 risk alleles compared to those having 3 - 6 risk alleles (P=0.00002). An association was also detected between the VEGF -2578A/C polymorphism and CS gain (P=0.014). During the first year VA change correlated negatively with the number of visits when cystic changes were detected in the OCTs (r=-0.366, P=0.009), but the association did not persist during the second year. Conclusion VEGF -2578A/C, IL-8 -251A/T, and CFH Y402H seem to to affect the persistence of fluid in the macular area during bevacizumab therapy of exudative AMD.

Purpose To study the association of potential key single-nucleotide polymorphisms with the short-term anatomic response to bevacizumab treatment in exudative age-related macular degeneration (AMD). Methods Clinical data 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. Representative single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes were analysed. Results Interleukin 8 promoter polymorphism −251A/T,conferring a more acitve interleuking-8 system, 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 a poorer outcome. Conclusion The interleukin -8 pathway may modulate the early anatomic response to anti-VEGF treatment in AMD. A possible activation of interleukin -8 production in patients may represent a compensatory mechanism to chronic blockade of VEGF signalling in AMD lesions

Purpose Evaluation of ocular tissue reactions to 670-nm diode laser. Methods Twelve eyes of 12 pigmented rabbits were used. Transscleral contact laser delivery of a new 670-nm diode laser was used to produce retinal laser lesions in four rabbits; endolaser application of this laser produced photocoagulation of the retina in another four rabbits; and ciliary body lesions were produced by transscleral application of this laser in a third group of four rabbits. The rabbits were killed either 2 days or 1, 3, or 6 weeks later; lesions were evaluated by gross examination and histology. Results The mildest visible retinal lesions were produced by transscleral contact application at 0.2 J (2 seconds, 100 mW); explosive lesions began at 0.6 J. The mildest visible lesions were produced by endolaser application at 50 mW (spot size, 0.5 mm); intensive reactions started to occur at 300 mW, but no explosive lesions were produced below 600 mW. With contact transscleral application, substantial ciliary body reactions occurred at 0.5 and 1.0 J. Histologic examination disclosed destruction of the outer retina, pigment epithelium, and parts of the choroid in mild lesions, and of all retinal layers in the intense lesions. Conclusions In this experimental study, the 670-nm diode laser appears to be a promising modality for laser photocoagulation of the retina and ciliary body.