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.

Retinal arterial macroaneurysms.

Retinal arterial macroaneurysms are acquired saccular or fusiform dilatations of the large arterioles of the retina, usually within the first three orders of bifurcation. They are associated with systemic vascular conditions such as hypertension and arteriosclerotic disease occurring most commonly in elderly women. The primary reported symptom is a sudden loss of vision due to haemorrhage or oedema affecting the macula. Most of macroaneurysms regress without treatment and without causing decreased visual acuity. Poor visual outcome may occur secondary to foveal exudates and subfoveal haemorrhage.

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.

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.

Photodynamic therapy with verteporfin to induce regression of aggressive retinal astrocytomas.

PURPOSE: To evaluate the effect of photodynamic therapy (PDT) with verteporfin on symptomatic, aggressive retinal astrocytomas. METHODS: A prospective, interventional study in a tertiary referral centre. Two patients were treated with a single session of PDT using the standard parameters of the Verteporfin in Photodynamic Therapy (VIP) study: a 34-year-old man whose previously stationary juxtapapillary retinal astrocytoma, secondary to tuberous sclerosis, progressed within 7 months to involve the foveola; and a 68-year-old man whose acquired retinal astrocytoma progressed over 18 months in spite of standard photocoagulation. Both tumours were vascularized and had caused secondary lipid exudation and an exudative retinal detachment. Outcome measures were visual acuity, resorption of subretinal fluid, tumour height and fluorescein angiography. RESULTS: The progressing, vascularized part of both retinal astrocytomas regressed, with little change in the poorly vascularized, stationary part of the congenital hamartoma. Visual acuity improved in the first patient and was unchanged in the second by 3 months, with stable vision in both and no sign of recurrence at 2 years. The exudative retinal detachments resolved completely. Tumour height reduced a median of 30%. Regression was associated with obliteration of tumour vessels within the progressing part of the lesion, with closure of some of the dilated retinal capillaries over the tumour. Intraretinal microvascular abnormalities and scattered haemorrhages appeared outside the treated area in the first patient. CONCLUSION: PDT with verteporfin can induce regression of progressive, vascularized, aggressive retinal astrocytomas and may prevent typical progression to total retinal detachment and enucleation, whether the astrocytoma is associated with tuberous sclerosis or not. PDT may be considered a first-line treatment for aggressive retinal astrocytomas.

Complement factor H Y402H polymorphism and characteristics of exudative age-related macular degeneration lesions.

PURPOSE: The Y402H polymorphism of the complement factor H (CFH) gene is associated with age-related macular degeneration (AMD) in many populations. The reported genotype-phenotype correlations in the CFH Y402H polymorphism have not been pronounced and no studies on the effect of the polymorphism on the subgroups within wet AMD have been performed. In this study, we wanted to evaluate whether the CFH Y402H polymorphism has an effect on clinical variables in recent exudative AMD lesions. METHODS: The study included 172 patients with exudative AMD. The size of AMD lesions and the presence and area of other AMD lesion variables were recorded in fluorescein angiography (FA) and analysed in relation to the Y402H genotypes. RESULTS: The median lesion size (classic + occult choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] + haemorrhage, if present) was 8.15 mm(2) in patients homozygous for the CFH risk allele (CC), 7.50 mm(2) in heterozygous patients (CT), and 7.05 mm(2) in those with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV, combined, without serous PED or haemorrhage were 6.37 mm(2), 5.00 mm(2) and 5.18 mm(2), respectively (p = 0.407). There was a trend for CC patients to have more frequently minimally classic and less frequently predominantly classic lesion composition than CT or TT subjects. CONCLUSIONS: We detected no clear impact of the CFH Y402H polymorphism on recent exudative AMD lesion characteristics. Although the complement cascade is implicated in CNV formation and scarring processes in the retina, the Y402H polymorphism appears relatively neutral in these functions.

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.

Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population.

PURPOSE: A strong association of a Tyr402His polymorphism in the complement factor H (CFH) gene and a Met299Val polymorphism in the elongation of very long chain fatty acids-like 4 (ELOVL4) gene with age-related macular degeneration (AMD) has been identified in Caucasian populations in the United States. Earlier a Gln5345Arg variant in the hemicentin 1 (HMCN1) gene was reported in a large AMD family in the United States. We wanted to investigate whether the polymorphisms of the CFH and the ELOVL4 genes or the mutation of the HMCN1 gene are associated with AMD in patients originating from the Finnish population with characteristics of a genetic isolate. METHODS: The material consisted of familial (n=181) and sporadic cases (n=154) with AMD, a control group with no AMD (non-AMD controls, n=105), and a control group of anonymous blood donors (blood donor controls, n =350). The DNA of the subjects was sequenced to analyze the variants of the three genes. RESULTS: We detected a strong association between the C/C-genotype compared to the T/T-genotype of Tyr402His polymorphism (first base of the Tyr-codon changes) of the CFH gene and AMD in the AMD cases compared to the non-AMD (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)). The frequency of the C/C genotype was significantly increased in both familial cases compared to non-AMD controls with non-adjusted odds ratio (OR) 10.1 (confidence intervals [CI] 95% 4.64-22.2) or compared to blood donor controls with non-adjusted OR 5.50 (CI 95% 3.17-9.55) and in sporadic cases with non-adjusted OR 9.33 (CI 95% 4.10-21.3; non-AMD-controls), OR 5.06 (CI 95% 2.75-9.28; blood donor controls). Frequency of C allele differed significantly between cases and controls (p=1.32x10(-11); non-AMD-controls and p=3.94x10(-14); blood donor controls). No association with AMD was detected with Met299Val polymorphism in the ELOVL4 gene in the familial or sporadic cases compared to non-AMD or blood donor controls. None of our subjects (258 AMD cases, 72 non-AMD controls) had the Gln5345Arg variant in the HMCN1 gene. CONCLUSIONS: The CFH gene polymorphism seems to be an important etiologic factor for AMD also in the isolated Finnish population.

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.

Fungal endophthalmitis caused by Paecilomyces variotii following cataract surgery: a presumed operating room air-conditioning system contamination.

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.

Retinal breaks and detachment after neodymium: YAG laser posterior capsulotomy: five-year incidence in a prospective cohort.

PURPOSE: To determine the 5-year incidence of retinal breaks and retinal detachment (RD) after neodymium:YAG (Nd:YAG) laser posterior capsulotomy and the prophylactic treatment of perioperative retinal breaks. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: This study design was stage 2 of a prospective nonrandomized interventional case series. Of 341 patients (350 eyes) referred for a first Nd:YAG laser posterior capsulotomy between October 1994 and February 1996, 211 (220 eyes) were examined for retinal breaks before and after capsulotomy (stage 1 of study). Asymptomatic breaks were prophylactically photocoagulated. Of the 211 patients, 106 (113 eyes) were examined at stage 2 a median of 4.9 years after Nd:YAG capsulotomy. The charts of all 341 patients were reviewed for development of RD and retinal breaks. The proportion of patients developing RD was estimated by Kaplan-Meier survival analysis, and the risk for RD was modeled by Cox proportional hazard regression. RESULTS: By 5 years, the overall cumulative proportion of RD in the 341 patients was 2.0% (95% confidence interval [CI], 1.0-4.0). Of the 211 eyes enrolled in stage 1, 2 (1.2%) developed an RD (95% CI, 0.3-4.7). Of 51 fellow eyes that had a capsulotomy and 120 eyes that had a capsulotomy but were not enrolled in stage 1 and were not prophylactically treated, RD occurred in 6 eyes (5.8%; 95% CI, 2.6-13). By univariate Cox regression, the axial length, whether modeled as a continuous variable (hazard ratio [HR] 1.51 for each millimeter increase) or categorized using 25.0 mm as a cutoff (HR 11.1), had the strongest association with RD after Nd:YAG posterior capsulotomy (P =.0002 and P =.0016, respectively). CONCLUSIONS: In addition to the capsulotomy, other known risk factors predicted RD after Nd:YAG laser posterior capsulotomy. Close follow-up and prophylactic photocoagulation of preexisting retinal breaks are worth considering, especially in high-risk eyes.

Stereotactic radiotherapy of symptomatic circumscribed choroidal hemangiomas.

PURPOSE: To determine feasibility of low-dose stereotactic radiotherapy in the treatment of symptomatic circumscribed choroidal hemangioma. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Five consecutive patients with perifoveolar and peripapillary circumscribed choroidal hemangioma and visual symptoms from exudative retinal detachment. METHODS: A dose of 20 Gy was delivered stereotactically with linear accelerator. Tumor dimensions were determined by B-scan ultrasonography. MAIN OUTCOME MEASURES: Resolution of subretinal fluid, best-corrected visual acuity, and reduction in tumor height. RESULTS: Median tumor height at baseline was 2.8 mm (range, 2.0-4.2 mm). Two tumors were subfoveolar, two were juxtafoveolar, and one was extrafoveolar. Cystic macular edema and subretinal fibrosis were present in both eyes with subfoveolar tumor. Exudative retinal detachment resolved within a median of 5 months (response rate, 100%; 95% CI, 48%-100%). Median best-corrected visual acuity was 20/50 (range, 20/22-20/100) at diagnosis and 20/25 (range, 20/20-20/60) 20 months after treatment. Tumor height had decreased a median of 24% (range, 0%-31%) by 6 months and 29% (range, 9%-59%) by 20 months. Secondary retinal pigment epithelial mottling associated with tumor regression occurred in two patients. One eye developed a paracentral scotoma. CONCLUSIONS: Stereotactic radiotherapy can be targeted precisely enough to induce regression of subretinal fluid from circumscribed choroidal hemangiomas.