Type Of Choroidal Neovascularization Research Articles

RETINAL ANGIOMATOUS PROLIFERATION DIAGNOSIS: A Multiimaging Approach.

To identify signs occurring more frequently in retinal angiomatous proliferation (RAP) lesions compared with other types of choroidal neovascularization (CNV) in age-related macular degeneration. In this cross-sectional retrospective study, 30 patients were evaluated. These signs were correlated with the type of CNV: shunting of blood flow to the lesion by fluorescein angiography, late leakage by indocyanine green angiography, intraretinal cysts and retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment with a hyperreflective oval area by spectral domain optical coherence tomography, and presence of reticular pseudodrusen by infrared light. Shunting of blood flow was found in 56% of RAP, whereas it was absent in 100% of other CNVs. Late leakage in indocyanine green angiography occurred in all RAP cases, while it was found in 7% of other CNVs. Intraretinal cysts were detected in 100% of RAP cases and in 14% of other CNVs. Retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment was evident in 93% of RAP cases and in 15% of other CNVs. Reticular pseudodrusen were present in 87% of RAP cases and in 21% of other CNVs. All the signs investigated were strongly associated to RAP lesions. A multimodal imaging approach may help differentiating subtypes of neovascularization.

Single-Nucleotide Polymorphisms Associated With Age-Related Macular Degeneration and Lesion Phenotypes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

Single-nucleotide polymorphisms (SNPs) associated with the CFH, ARMS2, C3, LIPC, CFB, and C2 genes are associated with age-related macular degeneration (AMD); however, the association of these SNPs with angiographic features of neovascular AMD has been inconsistent in previous studies, and to date, no studies have addressed their association with features on optical coherence tomography. To evaluate the influence of genotype of SNPs previously associated with AMD on the phenotype of neovascular lesions. Participants for this cross-sectional study were recruited from the 1185 patients enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), a randomized clinical trial. Eligibility criteria for CATT specified that eyes have choroidal neovascularization and visual acuity between 20/25 and 20/320. A subgroup of 835 patients provided blood samples from July 2010 through September 2011 and were genotyped for the SNPs rs1061170 (CFH), rs10490924 (ARMS2),rs2230199 (C3), rs10468017 (LIPC), rs4151667 (CFB), rs547154 (C2) using TaqMan SNP genotyping assays. Data analysis was initiated in November 2013 and completed in January 2016. Pretreatment ocular characteristics on fluorescein angiography (lesion type, area of neovascularization and total lesion, retinal angiomatous proliferation) and on time-domain optical coherence tomography (presence of intraretinal, subretinal, and subretinal pigment epithelium fluid; thickness at the foveal center of the retina, subretinal fluid, and subretinal tissue complex), visual acuity, and age. A total of 835 (73%) of 1150 CATT patients were genotyped. Mean age decreased with the number of risk alleles for CFH (P < .001), ARMS2 (P < .001), and C3 (P = .005). The following results were found as the number of risk alleles increased from 0 to 1 to 2. For CFH, mean total thickness decreased from 476 to 476 to 434 µm (P = .01; adjusted for age, sex, and smoking status). For ARMS2, the mean area of the total lesion increased from 2.0 to 2.8 to 2.4 mm2 (P = .03), the proportion with retinal angiomatous proliferation lesions increased from 8% to 10% to 12% (P = .05), and the proportion with intraretinal fluid increased from 72% to 71% to 82% (P = .008). For C3, the proportion with intraretinal fluid decreased from 78% to 69% to 64% (P = .001), and the mean retinal thickness decreased from 225 to 207 to 197 µm (P = .02). CFH, ARMS2, and C3 were associated with specific features of neovascularization at the time patients were enrolled in CATT. Previously identified associations of ARMS2 and CFH with type of choroidal neovascularization on fluorescein angiography were not confirmed. New associations with OCT features identified in CATT need confirmation to establish whether a true association exists. clinicaltrials.gov Identifier: NCT00593450.

OCT angiography for exudative age-related macular degeneration : Initial experiences

The new technique of optical coherence tomography (OCT) angiography allows a non-invasive reconstruction of the three-dimensional structure of the total retinal and choroidal vascularization within seconds. There are still limitations caused by movement artefacts, superimposition of superficial retinal vessels at the retinal pigment epithelium (RPE) level and insufficient three-dimensional imaging modalities. Initial experiences with this new method and especially the correlation with the current standard diagnostic procedure of fluorescein angiography show that new information can be obtained regarding specific vascular and neovascular changes. For three-dimensional neovascular changes, such as those found in exudative age-related macular degeneration (AMD,) a more sophisticated diagnostic analysis strategy must be specifically developed. Initial experiences demonstrate that the differentiation into the various types of choroidal neovascularization (CNV) by fluorescein angiography, specifically for type 1 (occult) and type 2 (classical) can also be visualized by OCT angiography. Furthermore, the new technology provides additional information on the choroidal and outer retinal changes associated with this disease, which may result in a better understanding of the underlying pathology.

Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

PurposeTo describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision.MethodsThis was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed.ResultsEyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased.ConclusionsFAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular endothelial growth factor therapy regardless of CNV lesion type.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VERSUS TRADITIONAL MULTIMODAL IMAGING IN ASSESSING THE ACTIVITY OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION: A New Diagnostic Challenge.

To compare optical coherence tomography angiography (OCTA) with traditional multimodal imaging in patients with exudative age-related macular degeneration in terms of guiding the treatment decision. Prospective case series of 80 eyes of 73 consecutive patients with exudative age-related macular degeneration (39 women, mean age: 79.4 ± 5.3 years) diagnosed with different types of choroidal neovascularization (CNV) (58 Type I, 2 Type II, 6 mixed Type I and II, 3 retinal angiomatous proliferation, and 11 age-related macular degeneration-related polyps). The data obtained from traditional multimodal imaging, based on fluorescein angiography, indocyanine green angiography, and OCT were used to assess the need for treatment, those obtained from OCTA to identify two different patterns of CNV. Traditional multimodal imaging and OCTA findings were then compared with evaluate possible correspondence between treatment decision and CNV aspect on OCTA. A CNV lesion was identified as Group A (requiring treatment) in 58 eyes (72.5%) in traditional multimodal imaging. On OCTA in 59 eyes (73.7%), the lesion was defined as Pattern I and the remaining 21 (26.3%) as Pattern II. There was 94.9% correspondence between the Pattern I CNV on OCTA and the cases Group A on conventional multimodal imaging. It was also computed 90.5% correspondence between Pattern II CNV on OCTA and the Group B (not requiring treatment) cases on conventional multimodal imaging. There was high (P < 0.05) interobserver agreement both for treatment decision in conventional multimodal and for Patterns (I or II) defining on OCTA imaging analysis. This study demonstrates a high level of correspondence, in patients with exudative age-related macular degeneration, between different CNV patterns identified on OCTA and treatment decisions established on conventional multimodal imaging. Although fluorescein angiography remains the gold standard for determining the presence of leakage, and OCT shows fluid accumulation and its variations, OCTA may now offer noninvasive monitoring of the CNV, aiding for each treatment decision during the follow-up.

Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration.

PurposeTo investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD).MethodsA total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed.ResultsAge, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV.ConclusionsOnly one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.

Anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy with polyps resembling grape clusters.

The objective of this study was to investigate the 2-year outcomes of treatment with anti-vascular endothelial growth factor (VEGF) in patients with polypoidal choroidal vasculopathy (PCV) with polyps resembling grape clusters. Twenty eyes in 20 patients were included. All patients initially received three consecutive anti-VEGF injections, followed by an as-needed re-injection schedule. Patients were followed regularly at 1- to 3-month intervals. The primary outcome was change in best-corrected visual acuity (BCVA). The mean number of injections administered over the course of 24months was 12.50 ± 2.77 (range, 9-18). The logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.61 ± 0.28 to 0.42 ± 0.27 at 12months (P = 0.015), and 0.44 ± 0.31 at 24months (P = 0.056). At 24months, BCVA had improved in 6 (30.0%) eyes by 0.3 logMAR or more, was stable in 11 (55.0%) eyes, and had decreased in 3 (15.0%) eyes. Complete absorption of fluid was achieved with anti-VEGF treatment in 18 (90%) eyes at least once during the 2-year follow-up period, and 10 (50%) eyes revealed a dry macula at 24months. Two eyes (10.0%) received rescue photodynamic therapy because subfoveal fluid persisted despite six and seven consecutive anti-VEGF injections. Of 18 eyes treated only with anti-VEGF agents, 3 (16.7%) revealed partial resolution of the polypoidal lesions at 24months. A treatment regimen with anti-VEGF effectively improved or maintained visual acuity over a 24-month period in patients with PCV with clusters of grape-like polyps, and required frequent injections, comparable to typical choroidal neovascularization in age-related macular degeneration.

CORRELATION OF FOVEAL MICROSTRUCTURAL CHANGES WITH VISION AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN AGE-RELATED MACULAR DEGENERATION

To investigate the correlation of foveal microstructural changes with vision after intravitreal ranibizumab injection in eye with choroidal neovascularization (CNV) secondary to age-related macular degeneration. We retrospectively studied 40 eyes of 40 patients with neovascular age-related macular degeneration who had no previous treatment history of age-related macular degeneration. All patients were treated with 3 monthly intravitreal ranibizumab (0.5 mg/0.05 mL) injections. One month after the third consecutive injection, best-corrected visual acuity (BCVA) was evaluated and the eyes were categorized into 2 groups according to the change in BCVA (good function group: BCVA improvement ≥ logarithm of minimum angle of resolution 0.3; poor function group: BCVA improvement < logarithm of minimum angle of resolution 0.3). Changes of foveal photoreceptor layer integrity, CNV size (diameter and thickness), central macular thickness, center point thickness, outer nuclear layer thickness, and subretinal fluid in each group were also evaluated using spectral-domain optical coherence tomography. The good function group is 20 eyes, and the poor function group is 20 eyes. No significant differences in baseline characteristics of variables including CNV type, initial BCVA, photoreceptor integrity, and CNV size were observed between the two groups. Best-corrected visual acuity in the good function group was 0.30 ± 0.17 (logarithm of minimum angle of resolution) and that in the poor function group was 0.48 ± 0.40 (logarithm of minimum angle of resolution). Decreased disrupted length of photoreceptor layer (1,020.80 ± 974.60) and decreased CNV thickness (78.86 ± 50.78) were found in the good function group at the end of follow-up. However, no significant differences in changes of CNV diameter, central macular thickness, center point thickness, outer nuclear layer thickness, and resolution of subretinal fluid were observed between the two groups. Restoration of foveal photoreceptor integrity and decreased CNV thickness are closely associated with visual improvement in neovascular age-related macular degeneration after treatment.

The effect of intravitreal ranibizumab injection on visual acuity and central macular thickness in subgroups with neovascular age-related macular degeneration

In this study, we assessed the effect of at least three intraocular ranibizumab injections, which were performed for the treatment of subfoveal choroidal neovascularization (CNV) secondary to neovascular age related macular degeneration (AMD), on best corrected visual acuity (VA) and central macular thickness (CMT) in 89 patients who were classified by the component of lesion. Flouroscein angiography was performed and CNV have been classified in classic, occult or mixt (classic+occult) type. Best corrected VA was measured by Snellen card and was recorded in logMAR-logarithm of the minimum angle of resolution values. CMT was measured by optical coherence tomography. While CMT decreased significantly in patients with classic, mixt or occult type lesion (p=0.000; 0.011; 0.004, respectively), the increase in VA was detected only in patients with classic type lesion (p=0.001). A positive significant correlation between the decrease in CMT and the decrease in VA (logMAR) was reported only in the patients with occult type lesion (p=0.03). In conclusion, the anatomical improvement, that is seen as a result of the treatment of AMD with intravitreal ranibizumab injection, is not associated with the increase in visual acuity in all types of CNV. J. Exp. Clin. Med., 2013; 30:1-3

Segmentation of Choroidal Neovascularization in Fundus Fluorescein Angiograms

Choroidal neovascularization (CNV) is a common manifestation of age-related macular degeneration (AMD). It is characterized by the growth of abnormal blood vessels in the choroidal layer causing blurring and deterioration of the vision. In late stages, these abnormal vessels can rupture the retinal layers causing complete loss of vision at the affected regions. Determining the CNV size and type in fluorescein angiograms is required for proper treatment and prognosis of the disease. Computer-aided methods for CNV segmentation is needed not only to reduce the burden of manual segmentation but also to reduce inter- and intraobserver variability. In this paper, we present a framework for segmenting CNV lesions based on parametric modeling of the intensity variation in fundus fluorescein angiograms. First, a novel model is proposed to describe the temporal intensity variation at each pixel in image sequences acquired by fluorescein angiography. The set of model parameters at each pixel are used to segment the image into regions of homogeneous parameters. Preliminary results on datasets from 21 patients with Wet-AMD show the potential of the method to segment CNV lesions in close agreement with the manual segmentation.

FUNDUS AUTOFLUORESCENCE NOT PREDICTIVE OF TREATMENT RESPONSE TO INTRAVITREAL BEVACIZUMAB IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION

Foveal autofluorescence (AF) has been suggested to be a potential predictor of treatment outcome in choroidal neovascularization (CNV) secondary to age-related macular degeneration and could be a useful marker to help prognosticate for patients and for clinical trials. This retrospective study aims to determine if pretreatment foveal AF can predict treatment response to intravitreal bevacizumab monotherapy in CNV secondary to age-related macular degeneration. Ninety-five eyes (85 patients) with naive CNV secondary to age-related macular degeneration, treated with intravitreal bevacizumab monotherapy were included in this study. Lesion size, CNV type on fluorescein angiography, pretreatment best-corrected visual acuity, and foveal AF pattern (intact/nonintact) were used as predictors. Multivariate linear regression and logistic regression were performed using best-corrected visual acuity change and anatomical response at 6 months as the dependent variables separately. Pretreatment foveal AF (intact or nonintact) did not predict visual outcome (P = 0.17) nor did lesion size (P = 0.2) or CNV type (P = 0.61). Foveal AF did correlate with the visual acuity but it did not predict any treatment response. Pretreatment best-corrected visual acuity was the only predictive factor for the visual outcome (P = 0.043). Pretreatment AF is not a predictor for the treatment response to intravitreal bevacizumab monotherapy in eyes with CNV secondary to age-related macular degeneration.

CAUSES OF UNSUCCESSFUL RANIBIZUMAB TREATMENT IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION IN CLINICAL SETTINGS

To identify the causes of loss of vision after ranibizumab therapy in patients with exudative age-related macular degeneration treated in three clinical settings. A retrospective multicentric analysis of 290 consecutive eyes comprising cohorts from 3 clinical settings showed that 21 eyes lost ≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart 1 year after the start of ranibizumab treatment. Fundus images of these eyes were analyzed by two independent readers to investigate the causes of visual loss. The three cohorts were compared. A search was made for factors predisposing to visual loss. A second analysis was performed to compare the baseline characteristics of patients who gained (visual acuity gainers) or lost (visual acuity losers) ≥ 15 letters. Among the 290 eyes included, the proportions from each center experiencing visual loss were not significantly different (mean, 7.24%, P = 0.2631). Mean visual loss of affected eyes was 27 letters. There was no significant difference between these eyes and others as regards age and gender of patients, laterality, type of choroidal neovascularization, number of visits, or initial visual acuity. Visual loss was secondary to the progression of atrophy in eight eyes, fibrosis in five eyes, a combination of fibrosis and atrophy in three eyes, severe subretinal hemorrhage in three eyes, and retinal pigment epithelial tear in two eyes. A significant difference between visual acuity gainers and losers was observed for 2 parameters: age of patients, 80.9 ± 5.3 years in visual acuity losers versus 77.5 ± 7.3 years in visual acuity gainers (P = 0.0473) and visual acuity at diagnosis, respectively, 56.2 ± 11.2 versus 49.0 ± 12.0 (P = 0.0288). Although uncommon, visual loss may occur during ranibizumab treatment and is because of the natural course of age-related macular degeneration in most cases.

Clinical management of a patient with polypoidal choroidal vasculopathy

Clinical management of a patient with polypoidal choroidal vasculopathy Todd PeabodyIndiana University School of Optometry, Bloomington, IN, USAAbstract: Polypoidal choroidal vasculopathy (PCV) is an often-misdiagnosed condition affecting the choroidal vasculature and retina of the posterior pole. The clinical identity of PCV was understood fully only recently, but shows unique demographics, clinical findings, and outcomes. Clinically, PCV can be confused with typical choroidal neovascularization and other diseases of the choroid, but generally shows a more favorable outcome. It is important to make the distinction between PCV and other diseases to ensure that patients are treated properly and not exposed to unnecessary procedures. This case report reviews the clinical findings and management of a patient with PCV as well as other studies, demographics of PCV, and current management options for patients with PCV.Keywords: polypoidal choroidal vasculopathy, retinal pigment epithelium detachment, indocyanine green angiography

Responses to Photodynamic Therapy in Patients With Polypoidal Choroidal Vasculopathy Consisting of Polyps Resembling Grape Clusters

To investigate the responses to photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV) that show large aneurysmal dilation with internal angio-architecture consisting of diverse patterns of curvilinear vessels and polyps resembling grape clusters. Retrospective, interventional case series. Twenty-two eyes of 22 patients were included. All patients initially received PDT monotreatment. The main outcome measures were the rates of complete polyp regression on indocyanine green angiography and initial favorable responses observed clinically. Also, the rates of recurrent exudative changes were evaluated at the 2-year follow-up. We focused on changes in the vascular features and their clinical association. Complete regression of polypoidal lesions was observed in 21 eyes (95%) after a mean of 1.7 PDTs. However, favorable clinical responses were achieved in only 9 eyes (41%), and 6 of them had recurrent exudation. Main vessels, previously consisting of the polypoidal lesion frame, persisted. Additionally, aberrant vessels with a thin radiating or tortuous configuration were observed in the area where large aneurysmal dilation was present. Leakage from this vascular complex or an expanded vascular complex was observed in a total of 14 eyes (64%) during the 2-year follow-up, contributing to persistent (8 eyes) or recurrent (6 eyes) exudation. This seemed to represent secondary choroidal neovascularization (CNV). In another 4 eyes (18%), fibrous changes developed immediately after PDT. Polyps recurred in 8 eyes (38%). This PCV pattern frequently evolved into typical CNV after PDT, resulting in persistent or recurrent exudation despite the disappearance of polypoidal structures.

Evaluation of Changes in Choroidal Neovascularization Secondary to Age-related Macular Degeneration after Anti-VEGF Therapy Using Spectral Domain Optical Coherence Tomography

Purpose: To evaluate the changes in choroidal neovascularization (CNV) after anti-VEGF therapy for treatment of age-related macular degeneration (AMD) using spectral domain optical coherence tomography (SD OCT).Materials and Methods: This retrospective study included 65 eyes of 65 patients with CNV secondary to AMD. All patients underwent SD OCT before and 4 weeks after three intravitreal injections of bevacizumab (bevacizumab group) or ranibizumab (ranibizumab group). The diameter and thickness of CNV were measured from SD OCT images.Results: Retinal edema was completely resolved in 57%, partially resolved in 28% and unchanged in 15% of all post-injection SD OCTs. The resolution rate of retinal edema was not significantly different between the bevacizumab and ranibizumab group (p = 0.960). In all CNV types, the diameter of CNV did not show significant change after treatment; the average diameter changed from 2923 to 2888 μm in classic CNV and from 2378 to 2338 μm in occult CNV in bevacizumab group; from 2691 to 2580 μm in classic CNV and from 2731 to 2337 μm in occult CNV in ranibizumab group. However, the thickness of CNV showed a significant reduction in classic CNV of both the bevacizumab group (from 301 to 233 μm, p = 0.012, reduction rate 22%) and the ranibizumab group (from 258 to 213 μm, p = 0.025, reduction rate 17%). In occult CNV, the thickness of CNV showed a significant reduction only in the ranibizumab group (from 163 to 146 μm, p = 0.033, reduction rate 10%).Conclusions: Anti-VEGF therapy for the treatment of AMD may reduce the thickness of CNV and thus result in morphologic stability of CNV. Although morphologic regression of CNV is not achieved, further CNV growth could be arrested with anti-VEGF therapy.

Associations of Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) Genotypes with Subtypes of Polypoidal Choroidal Vasculopathy

To clarify whether complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes are associated with subtypes of polypoidal choroidal vasculopathy (PCV), such as polypoidal choroidal neovascularization (CNV) and typical PCV. Two hundred eighty-seven patients were categorized as having polypoidal CNV (85 patients) or typical PCV (202 patients) on the basis of indocyanine green angiographic findings. In total, 277 subjects without age-related macular degeneration (i.e., free of PCV and CNV), served as controls. I62V (rs800292) in the CFH gene and A69S (rs10490924) in the ARMS2 gene were genotyped, and case-control studies were performed in subjects with these PCV subtypes. The polypoidal CNV group included no subjects homozygous for the A/A genotype of rs800292, whereas 7% of the typical PCV group had this genotype. Case-control studies of polypoidal CNV and typical PCV showed significant differences in all distributions of rs10490924 between these two groups. In contrast, the distributions of rs10490924 did not differ between the typical PCV and control groups. Logistic regression analysis with adjustment for confounding factors showed the distributions of rs10490924 to differ significantly between the controls and polypoidal CNV cases (P = 2.1 × 10(-10); OR, 10.87). The T/T genotype was significantly more common in the polypoidal CNV than in the typical PCV group (P = 3.6 × 10(-14); OR, 19.61). PCV may be genetically divisible into polypoidal CNV and typical PCV. The rs800292 variant of the CFH gene is a potential marker for typical CNV. The rs10490924 variant of the ARMS2 gene was shown to be associated with polypoidal CNV. Typical PCV was not associated with this variant.

OCT in uveitis

AbstractPurpose To describe the role of optical coherence tomography (OCT) in uveitis.Methods The current literature is reviewed and the experience of a tertiary referral centre is reported.Results The involvement of the posterior pole during an active eye inflammatory disease can entail a reduction of visual acuity, which is sometimes difficult to treat. Albeit fluorescein angiography (FA) is still the gold standard for the detection of blood‐retinal barrier (BRB) disruption and has been the best option for the diagnosis of cystoid macular oedema (CMO), OCT represents an essential tool that can ameliorate the interpretation of FA findings. Epiretinal membrane (ERM) and tractional maculopathy may represent a sight‐threatening sequela of uveitis. OCT is extremely useful in documenting pathologies at the vitreo‐retinal interface, such as the formation of ERM, as well as it is also helpful in proving early infiltrates at the posterior vitreous interface. Although FA still remains the gold standard for the choroidal neovascularization (CNV) assessment, OCT is very helpful in documenting CNV nearby a chorioretinal scar. OCT has been used to study the type of CNV and to find its correlation to RPE.Conclusion OCT may demonstrate a variety of morphological changes, that may point towards a specific uveitic disease: different forms of macular oedema may be described in uveitis as well as OCT features which can be peculiarly found in several diseases. In addition, OCT can be very useful in documenting both ERM and CNV.

Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. Wet AMD includes typical choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV). The etiology and pathogenesis of CNV and PCV are not well understood. Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive. By transgenically expressing human HTRA1 in mouse retinal pigment epithelium, we showed that increased HTRA1 induced cardinal features of PCV, including branching networks of choroidal vessels, polypoidal lesions, severe degeneration of the elastic laminae, and tunica media of choroidal vessels. In addition, HTRA1 mice displayed retinal pigment epithelium atrophy and photoreceptor degeneration. Senescent HTRA1 mice developed occult CNV, which likely resulted from the degradation of the elastic lamina of Bruch's membrane and up-regulation of VEGF. Our results indicate that increased HTRA1 is sufficient to cause PCV and is a significant risk factor for CNV.

Étude préliminaire sur l’efficacité de trois injections intravitréennes de bevacizumab dans le traitement de la dégénérescence maculaire liée à l’âge exsudative

To evaluate intravitreal bevacizumab therapy for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).A retrospective review between June 2006 and May 2008 of patients with CNV secondary to AMD was conducted. All patients were treated with intravitreal injection of bevacizumab (1.25mg) once a month during a 3-month-period. The mean evaluation criteria were the best-corrected visual acuity (BCVA) logMar testing before and one month after the third injection. All eyes underwent an angiography and an optical coherence tomography before injections to define the activity and the type of CNV and then to evaluate the persistence of leakage (macular edema, subretinal fluid, and pigment epithelial detachment) after treatment. Then treatments were left to the investigator's discretion during the following six months.Seventy-one eyes of 66 patients were enrolled. There were 65% occult CNV, 20% classic CNV, and 15% combined. A significant improvement in BCVA was observed, from 0.88±0.57 to 0.77±0.60 (p=0.001), one month after the third injection. At this time, 57.7% of the eyes required a reinjection because of leakage persistence. A concomitant treatment with intravitreal triamcinolone injection and/or photodynamic therapy was necessary for 8% of nonresponder eyes. Six months after initial treatment, a complete resolution of exudative signs was not obtained for 33.8% of eyes. The average number of injections was 3.85±0.96 during the 9-month follow-up. BCVA stability was observed at 4, 6 and 9-month follow-ups (F(71.2)=1.54; p=0.46). Three complications occurred: one endophthalmitis, one retinal tear, and one vitreous hemorrhage secondary to a macular hemorrhage.Mean BCVA significantly improved at one month after three consecutive monthly intravitreal injections of bevacizumab. However, most eyes required a reinjection.In spite of improvement in BCVA, leakage of the CNV persisted in most eyes after three monthly intravitreal injections of bevacizumab. Then retreatment and sometimes concomitant treatment was necessary to obtain complete resolution of exudative signs and BCVA stability.

Clinical Evidence of Intravitreal Triamcinolone Acetonide in the Management of Age-Related Macular Degeneration

Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution of cataract. Nevertheless, cataract surgery may stimulate the development of CNV (result in stimulating CNV). However, in large, randomized, clinical trials on combination therapy of TA and PDT, visual acuity failed to show an improvement, even though the lesion size and subretinal fluid had decreased, compared to controls treated with PDT alone. Some authors reported an increased risk of developing macular atrophy after the combination therapy with IVTA and PDT. Reduction of the PDT fluence rate in association with the use of steroids resulted in reducing the risk of macular atrophy and in a better visual acuity outcome. The introduction of anti-VEGF-based drugs has revolutionized the treatment of AMD and has replaced all the previous therapies used for CNV. Visual improvement becomes an expectation in a higher proportion of patients, previously limited to minimizing vision loss. Anti-VEGF therapy also resulted in superior visual improvement compared to all types of combination therapy with IVT and PDT. Nevertheless, anti-VEGF monotherapy also has many limitations due to the need of repetitive treatments, increased costs and tachyphylaxis. Treatment regimens involving TA in combination therapy with anti-VEGF and PDT may preserve benefits for substantially longer periods. A question remains open on whether a combination treatment with anti-VEGF, triamcinolone and/or PDT may be a treatment option in patients with exudative AMD, by offering, with one cycle of therapy, functional VA benefits comparable to those observed with continued monthly anti-VEGF therapy. Further trials, of higher scientific significance, are needed to study the potential of these treatment options.