Presence Of Choroidal Neovascularization Research Articles

Predictive Role of Gene Polymorphisms Affecting Thrombin-Generation Pathway in Variable Efficacy of Photodynamic Therapy for Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) represents the leading cause of central blindness in developed countries. The majority of severe vision loss occurs in the neovascular form of AMD, generally characterized by the presence of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) and drugs acting against vascular endothelial growth factor are the most commonly employed treatments for AMD-related subfoveal CNV. The combined use of both these strategies is the most promising therapeutic approach towards this harmful disease. The therapeutic action of PDT-V depends to a photochemical perturbation of thrombo-coagulative processes within CNV. Predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of post-PDT-V benefit have been recently documented in Caucasian patients with neovascular AMD. Particularly, heterozygous A-allele carriers of factor V Leiden 1691 or prothrombin 20210 gene are characterized by a greater possibility to exhibit clinical benefit after PDT-V. Both mutations induce thrombophilia increasing the thrombin generation in plasma and, thus, they can consistently intensify the photothrombotic phase of the therapeutic CNV occlusion. In prospect, considering the different individual susceptibility to PDT-V, a preoperative assessment of the genotypic thrombophilic background could optimize the eligibility criteria of this intriguing treatment. This review summarizes some of the recent published patents on treatment of neovascular AMD, with a particular attention to PDT-V application in combined therapeutic modalities.

The International Classification System and the Progression of Age-Related Macular Degeneration

Purpose: To determine whether grading based on the International Classification (IC) for age-related macular degeneration (AMD) allows recognition of change during the progression of the disease. Methods: Stereoscopic color fundus photographs of 50 eyes of 25 patients with AMD and at least 5 years of review were graded in a random and masked fashion for changes over time in the characteristics of drusen, pigmentary changes, and end-stage disease, according to the system defined by the IC for AMD, by two independent graders (F.B.S., I.L.). Fundus images were also analyzed in time sequence for clinical changes by a senior grader (I.L.) and two ophthalmologists (A.C.B., T.P.) without access to the grading forms of the IC grading. Clinical change, as recorded by the IC grading and the individual analysis, were compared. Results: There was 97.8% (κ = 0.70) concordance in identification of change. In four cases, the clinical classification differed from the IC grading: Two cases of drusen and two of end-stage disease grading. Inter-observer agreement for the IC grading was 89.4% for predominant phenotype (κ = 0.84), 89.36–91.49% for presence of choroidal neovascularization (CNV) (κ = 0.79–0.83), 87.23–89.36% for geographic atrophy (GA) (κ = 0.62–0.74) and 55.32% for area covered by drusen (κ = 0.31). Conclusions: Overall, progression from earlier stages of AMD to either of the two forms of advanced AMD were reflected accurately by the IC grading in the vast majority of cases.

The role of factor h macular degeneration secondary to pathologic myopia

Abstract Purpose To compare the frequency of genes associated with age‐related macular degeneration (AMD), specifically the complement factor H alleles in patients with choroidal neovascularization (CNV) secondary to pathologic myopia (CNV). Methods Patients with pathologic myopia (defined as axial length > 25.50mm or ‐ 6.00 dpt) were examined. The presence of choroidal neovascularization was confirmed by clinical examination and fundus photography; fluorescein angiography and autofluorescence images were analyzed when available. DNA samples from all study subjects were screened for variants in the CFH genes, commonly associated with age‐related macular degeneration. Results Seventy‐three patients (47 female and 36 male; age 23 – 90 years; average: 59 years) were included into the study. Visual acuity ranged from 20/25 to count fingers in 1 meter. The frequency of the CFH Y402H as well as other common CFH polymorphisms in this cohort corresponded to that detected in the general population. Conclusion Factor h variants commonly associated with AMD and other forms of CNV may not play a causal role in neovascular complications of pathologic myopia.

Association between Complement Factor H Gene Polymorphisms and Neovascular Age-Related Macular Degeneration in Koreans

This study was undertaken to investigate the association between the complement factor H (CFH) gene and exudative age-related macular degeneration (AMD) in Korean patients. Genomic DNA was isolated from the peripheral leukocytes of patients with exudative AMD (n = 114) and control subjects (n = 187). The sole criterion for exudative AMD was the presence of choroidal neovascularization. Four single-nucleotide polymorphisms (SNPs: -275C>T, I62V, Y402H, and IVS15) located in promoter, exon 2, exon 9, and intron 15 of the CFH gene were genotyped by PCR-based direct sequencing. The frequency of the C allele of Y402H (AMD, 10.5%; control, 6.5%) was found to be lower in Koreans than in Caucasians. In the present study, the difference between the frequencies of Y402H in cases and control subjects did not reach statistical significance (P = 0.071). However, the frequencies of the major alleles of three SNPs (-275C>T, I62V, and IVS15) were significantly different in patients and control subjects, and these SNPs were found to be separately associated with an elevated risk of exudative AMD. Seven haplotypes were identified in Koreans. Haplotype analysis showed that two haplotypes (TGTG, CGTG) conferred significantly higher risks of exudative AMD (P = 0.013, 0.035), and one haplotype (CATA) was significantly protective (P < 0.001). In Korean subjects, CFH polymorphism appears to be a considerable hereditary contributor to exudative AMD. Y402H polymorphism which has been suggested to be a major risk factor of AMD in Caucasians was found to be only marginally associated with exudative AMD with low frequency, whereas three adjacent SNPs in the CFH gene were significantly associated with AMD in Koreans.

Autofluorescence Imaging in Age-Related Macular Degeneration Complicated by Choroidal Neovascularization: A Prospective Study

To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). Prospective, observational, consecutive case series. Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment.

Prognosis of untreated occult choroidal neovascularization

The aim of this investigation was to evaluate prognostic factors influencing the short-term prognosis of occult choroidal neovascularization (CNV). A consecutive series of 107 untreated occult CNV in 101 patients were evaluated in terms of the effect of their initial lesion characteristics, as determined with fluorescein angiography (FA), indocyanine green angiography (ICG-A) and optical coherence tomography (OCT), on the change in distance acuity, lesion size and retinal thickness over 1-3 months. Descriptive statistics, the Pearson Correlation Coefficient and a multiple linear regression analysis were applied to treat the data. A total of 107 eyes (101 patients) were examined. The study cohort consisted of 35 males and 66 females, with a mean age of 77.6 years. During the 3-month study period the mean distance acuity decreased from 67.0 to 63.2 letters; the mean size of the lesion increased from 16.1 to 18.4 mm(2); the mean maximum retinal thickness increased from 374.5 to 387.5 mum. Of the lesions, 59.8% included pigment epithelial detachments (serous or fibrovascular) and 29.9% retinal angiomatous proliferation. A better distance acuity at both visits for the entire study population correlated significantly with smaller lesions, as determined by FA and ICG-A (p < 0.0001), and a lower maximum retinal thickness, as determined by the OCT (p < 0.0001). A small and statistically insignificant change in distance acuity, lesion size and retinal thickness occurred over the 3 months of the study period. This reduced the ability of the study to examine the effect of baseline findings on outcome. Only two factors - the presence of a RAP lesion or the presence of CNV in the other eye - significantly and adversely affected the distance visual acuity at follow-up.

Photodynamic therapy in combination with intravitreal triamcinolone for myopic choroidal neovascularization

Editor, Photodynamic therapy (PDT) using verteporfin has been shown to be an effective treatment of subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and pathologic myopia. However, recent studies have suggested that PDT can induce collateral damage, especially to the choriocapillary layer (CCL) and retinal pigment epithelium (RPE), and that it paradoxically has angiogenic properties itself (Ruiz-Moreno & Montero 2003; Schmidt-Erfurth et al. 2003; Gelisken et al. 2004; Postelmans et al. 2004). In pathologic myopia, CCL and RPE may show progressive atrophy even without the presence of CNV. Therefore, especially in PDT of CNV due to pathologic myopia, the number of PDT sessions should be as few as possible. Intravitreal injections of triamcinolone acetonide (IVTA) have been shown to have angiostatic and antiexudative effects (Gillies et al. 2003; Jonas et al. 2003), and preliminary studies in AMD patients suggest that the combination of PDT and IVTA may reduce the number of PDT sessions necessary to occlude the neovascular complex and may be beneficial for patients who do not respond to PDT in the first sessions (Spaide et al. 2003; Rechtman et al. 2004). Theoretically, a combination of PDT and IVTA may be particularly advantageous in the treatment of myopic CNV, but this has not yet been reported. We report on a 35-year-old man with an anisometropic myopia (right eye − 4.5 D, left eye −17.0 D), who experienced the onset of metamorphopsia and a loss of visual acuity (VA) in the left eye from 0.7 to 0.3 due to subfoveal classic CNV (greatest linear dimension 600 µm). Visual acuity in the right eye was 1.0. He received PDT using verteporfin, which led to a rapid reduction of metamorphopsia and a slight increase in VA to 0.4. About 4 weeks later metamorphopsia recurred and VA dropped again. Fluorescein angiography showed reperfusion and leakage of the CNV. Altogether the subject received five PDT sessions at 10–12-week intervals with early postoperative temporary occlusion of the CNV, reduced metamorphopsia and VA increase, which were then followed by reperfusion of the CNV, increasing metamorphopsia and decreasing VA. During follow-up, ophthalmoscopy and fluorescein angiography revealed an increasing atrophy of the RPE and CCL, corresponding in size and shape to the PDT treatment spots. Visual acuity decreased to 0.08. At last, after giving informed consent, the patient received a sixth PDT session (at which point the greatest linear dimension of the CNV was 1800 µm), which was combined with an intravitreal injection of about 20 mg triamcinolone acetonide. The intravitreal injection was performed 2 weeks prior to the PDT; the injection technique has been described previously (Jonas et al. 2003). Over the 8 months since this last intervention, VA has stabilized at 0.125 in the absence of metamorphospia. Fluorescein angiography has shown staining of the lesion and a surrounding RPE window defect. Ophthalmoscopically and in optical coherence tomography no subretinal fluid has been detected. The lens shows signs of early posterior subcapsular cataract development. At present, PDT is the therapy of choice for subfoveal classic CNV due to myopia. However, its biological effects (Schmidt-Erfurth et al. 2003) may induce a lesion reperfusion and growth, and additional damage to the RPE and CCL may occur with increasing numbers of PDT sessions. Highly myopic patients are especially susceptible to this PDT-induced damage, which may override the beneficial effects of the treatment in either the short or the longterm. The present case report suggests that a combination therapy of PDT plus IVTA may be beneficial in myopic patients who do not respond to PDT alone. Furthermore, it suggests that the side-effects of PDT (in terms of the temporary increase in the expression of angiogenic growth factors and collateral damage to the RPE) may be reduced, and as a corollary, the number of re-treatments may be decreased by combining PDT with intravitreal triamcinolone acetonide. The possible benefits of a combination therapy may outweigh the risks of IVTA. Further studies are warranted.

Retinal microangiopathies overlying pigment epithelial detachment in age-related macular degeneration.

To evaluate alterations in the retinal vasculature overlying pigment epithelial detachments (PED) in exudative age-related macular degeneration (ARMD) using indocyanine green and fluorescein angiography. Forty-one patients (41 eyes) with a clinical diagnosis of exudative ARMD with PED underwent simultaneous fluorescein and indocyanine green angiography, also under high (10 degrees ) magnification. Vascular abnormalities in the retina were compared between patients with vascularized (n = 34, group 1) and nonvascularized (n = 7, group 2) PED on indocyanine green angiography and correlated with the size of the PED and the presence of serous retinal detachment. In all, 67 vascular abnormalities were found by indocyanine green angiography and only 22 by fluorescein angiography; this finding was statistically significant (P < 0.0001). The finding of retinal vasculopathy (32 patients in group 1 and two patients in group 2) was directly correlated with the presence of choroidal neovascularizations (P = 0.002). There was also a direct correlation between the presence of choroidal neovascularization and size of the PED (P = 0.03). The number of retinal vascular findings was not significantly correlated with serous elevation of the retina. Retinal vasculopathies may be observed in eyes with PED and are detectable by indocyanine green and fluorescein angiography.

Choroidal osteoma: an atypical presentation

Choroidal osteomas are benign osseous tumors of the choroid. These tumors typically occur unilaterally in the juxtapapillary region in young, healthy, white females. The fundus appearance is a yellow-white or orange-red elevated lesion with sharply demarcated irregular borders. Potential complications include growth and visual compromise secondary to choroidal neovascularization. Management involves photodocumentation with annual funduscopic examination and daily Amsler Grid self assessment. Laser photocoagulation is advocated in the presence of choroidal neovascularization within the arcades. A 70-year-old male presented with a unilateral subretinal elevated yellow-orange mass. Although atypical in presentation, the lesion was diagnosed as a choroidal osteoma based on the funduscopic appearance, computed tomography, ultrasonography and serologic testing.

Follow-up study of detachment of the retinal pigment epithelium.

To determine the clinical course of untreated retinal pigment epithelial detachment we reviewed data from 50 eyes of 42 patients followed up for an average of 29 months without photocoagulation. In 14 eyes with avascular lesions, in patients under 50 years of age, all had a final vision of 20/30 or better. None developed neovascularisation or haemorrhage. In 17 eyes with avascular lesions in patients aged over 50, 8 (47%) flattened spontaneously. Five (24%) developed neovascularisation, 2 of which became haemorrhagic, with vision of less than 20/200. In 19 senile eyes with vascular lesions 14 (74%) had a final vision of 20/200 or less. The prognosis in eyes with pigment epithelial detachments is related to the age of the patient and the presence of choroidal neovascularisation. Photocoagulation is seldom needed for pigment epithelial detachments in young patients. Its value in senile eyes is unproved.