Risk Factors For Choroidal Neovascularization Research Articles

Imaging Characteristics of Neovascular and Atrophic Pachychoroidal Spectrum Diseases.

BackgroundThis study qualitatively and quantitatively compared imaging characteristics between neovascular and atrophic pachychoroid spectrum disease (PSD) by optical coherence tomography (OCT), and OCT angiography (OCTA).MethodsThe subtypes of PSD were identified by multi-modality imaging approaches. Subfoveal choroidal thickness (SFCT), choroidal vascular index (CVI), and vascular density of choroidal neovascularization (CNV) were measured.ResultsThe CVI and SFCT of 174 PSD eyes were 67.6% ± 5.48% and 362.2 ± 131.88 μm, respectively. After adjustment for age, linear regression indicated that SFCT was positively associated with CVI (p < 0.001), and patched hyper-reflective lesions in choriocapillaris layers (p = 0.009). Compared with neovascular PSD eyes, atrophic PSD eyes had similar patient age (57.1 ± 16.72 years, p = 0.639), SFCT (332.0 ± 111.00 μm, p = 0.51), and CVI (67.6% ± 3.94%, p = 0.527). There were no differences between polypoidal choroidal vasculopathy (PCV) eyes with aneurysmal polypoidal lesions and PCV eyes with tangled polypoidal lesions in terms of age, CVI, SFCT, vascular density, or the occurrence of double layer signs (DLSs, all p > 0.05). Logistic regression indicated that age (p = 0.003), SFCT (p = 0.003), patched hyper-reflective lesions in choriocapillaris layers (p = 0.009), and DLSs (p < 0.001) were predictive factors for CNV progression in PSD eyes (all p < 0.05).ConclusionsOur study highlighted the similarities in SFCT and CVI between neovascular and atrophic PSD, both of which were late stage lesions. Besides, age, SFCT, patched hyper-reflective lesions in choriocapillaris layers, and DLSs were risk factors for CNV in PSD. Our results showed that atrophic PSD is an important change in the late stage of PSD disease, which is helpful for in-depth understanding of the pathological mechanism of PSD and corresponding intervention.

Clinical Features of Central Serous Chorioretinopathy With Type 1 Choroidal Neovascularization

To evaluate the type 1 choroidal neovascularization (CNV) incidence and associated factors in eyes with central serous chorioretinopathy (CSC). Retrospective case series. Records of 363 eyes (324 patients) with CSC were reviewed. Age, sex, CSC type, choroidal vascular hyperpermeability (CVH), best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), and systemic hypertension (HT) were assessed and compared between subjects with and without neovascular CSC. We identified 219 and 144 eyes with chronic and acute CSC, respectively. The mean participant age was 55.2 ± 12.0 years, and 58 (15.6%) eyes had neovascular CSC. Age (no CNV: 54.8 ± 12.1 years, CNV: 57.3 ± 10.9 years; P= .118) and SCT (no CNV: 388.0 ± 104.5μm, CNV: 377.4 ± 108.9μm; P= .487) were comparable between eyes with and without CNV. However, BCVA (logarithm of the minimum angle of resolution) was significantly worse in subjects with CNV (0.28 ± 0.33 [20/38] vs 0.15 ± 0.29 [20/28]; P= .014). Neovascular CSC occurred more often in women (72 [23.6%] vs 20 [34.5%], P= .099) and in cases of chronic CSC (171 [56.1%] vs 48 [82.8%], P < .001), CVH (205 [67.2%] vs 58 [100%], P < .001), and HT (91 [29.8%] vs 24 [41.4%], P= .092). Chronic CSC (P= .001), female sex (P= .075), and poor BCVA (P= .091) were associated with neovascular CSC (multiple regression). Chronic CSC, female sex, CVH, and poor BCVA are risk factors for CNV in eyes with CSC.

Vascularization of Irregular Retinal Pigment Epithelial Detachments in Chronic Central Serous Chorioretinopathy Evaluated With OCT Angiography.

To assess eyes with flat, irregular retinal pigment epithelial detachments (RPEDs) associated with central serous chorioretinopathy (CSCR) for choroidal neovascularization (CNV) using optical coherence tomography angiography (OCTA). Retrospective review of OCTA images of chronic CSCR eyes with irregular RPED (group 1) and regular RPED (controls, group 2) for presence of CNV, subretinal fluid, and intraretinal fluid. Fluorescein angiography was also evaluated for CNV. CNV was detected using OCTA in 13 of 31 eyes (41.9%) in group 1 and in one of 18 eyes (5.6%) in group 2 (P = .007). Irregular RPED was a risk factor for CNV (odds ratio [OR] = 12.28; 95% CI, 1.45-104.3). There was no significant difference between detection by OCTA and FA (P = 1.0). Sensitivity and specificity of detection by OCTA were 85.7% and 95.7%, respectively. Irregular RPEDs in chronic CSCR eyes may harbor neovascularization more often than previously thought, which has implications on therapy.

Understanding the determinants of myopic choroidal neovascularization and response to treatment.

The pathophysiologic pathways that govern the development of choroidal neovascularization (CNV) are complex. Patchy atrophy and lacquer cracks are known to be major anatomic risk factors for the development of myopic CNV, but they are not alone and much remains to be understood about other factors that influence development. In addition, a greater understanding of the modifiable and nonmodifiable factors that influence outcome, resolution, and recurrence after intravitreal injection of anti-vascular endothelial growth factor (VEGF) could lead to more personalized treatment algorithms that integrate parameters other than the presence of CNV itself and could help improve clinical outcomes and reduce recurrence. We reviewed recently published data on risk factors for CNV and predictors of response to anti-VEGF treatments. In particular, data pertaining to age, sex, genetic predisposition, baseline visual acuity, axial length, staphyloma, lacquer cracks, atrophic lesions, choroidal thickness or choroidal thinning, characteristics of CNV such as duration, localization, and size of CNV, and treatment considerations such as choice of treatment, loading doses, and combination treatments were reviewed. Our analysis showed that the body of evidence is incomplete. Additional studies are required to identify high-risk patients and to develop personalized therapeutic approaches.

Association of Risk Factors for Choroidal Neovascularization in Age-Related Macular Degeneration With Decreased Foveolar Choroidal Circulation

To investigate the relationship between known risk factors for age-related macular degeneration (AMD) progression and foveolar choroidal circulation in eyes with nonexudative AMD. Cross-sectional study of nonexudative AMD. Laser Doppler flowmetry measurements of relative choroidal blood velocity, choroidal blood volume (ChBVol), and choroidal blood flow (ChBFlow) were obtained in the center of the fovea of 273 study eyes of 204 AMD patients investigated at the Scheie Eye Institute, University of Pennsylvania Medical School. All study eyes had visual acuity of 20/40 or better, good fixation, no other intraocular pathologic features, and no evidence of choroidal neovascularization. RPE hypertrophy was determined from color fundus photographs by trained masked graders at the Scheie Image Reading Center. Correlation analysis and multivariate linear regression analysis with adjustments for significant covariates were carried out. A significant inverse correlation was observed between age and ChBFlow (r = -0.36; P < .0001), and ChBVol (r = -0.28; P < .0001), but not for choroidal blood velocity. A significant inverse correlation was observed between spherical equivalent and ChBFlow (r = -0.21; P = .006) and ChBVol (r = -0.14; P = .04), but not for choroidal blood velocity. ChBFlow and ChBVol were significantly lower in patients with a history of hypertension (P < or = .003) and in eyes with retinal pigment epithelium hypertrophy (P < or = .04), respectively. All the above-described risk factors for AMD development and progression are associated with decreased choroidal circulatory parameters, suggesting that decreases in choroidal circulatory parameters may be involved in the development of AMD.

Ocular Risk Factors for Choroidal Neovascularization in Pathologic Myopia

PURPOSE. To identify the risk factors for development of myopic choroidal neovascularization (mCNV), a major cause of visual impairment. METHODS. Enrolled in the study were 23 consecutive patients with bilateral high myopia (axial length, > or =26.5 mm or refractive error, < or =8 D) and unilateral newly developed mCNV who presented to the Myopia Clinic, Osaka University Hospital. Spectral-domain optical coherence tomography (SD-OCT) showed that the fellow eyes had a normal macula. The parameters in the affected and fellow eyes were compared between the individual patients, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), refractive error, axial length, choroidal thickness (CT) (subfoveal, 1.5 mm superiorly and inferiorly), posterior staphyloma height 3 mm from the fovea, length of retinal pigment epithelium (RPE) curvature within 6 mm measured on SD-OCT images, and choroidal degeneration and lacquer crack formation, graded according to a published RESULTS. The IOP, axial length, refractive error, and chorioretinal degeneration did not differ significantly. Affected eyes had a significantly higher lacquer crack grade (P < 0.05). The superior CT was not significantly different; the subfoveal and inferior CTs were significantly lower in the affected eyes (P < 0.05 and P < 0.001, respectively). The absolute value of the nasal posterior staphyloma height from the fovea was significantly greater in the affected eyes (P < 0.05), and the affected eyes had a significantly (P < 0.05) longer RPE curvature. CONCLUSIONS. Choroidal thinning resulting from increased RPE/choroid curvature is a risk factor for unilateral mCNV.

Posterior Vitreomacular Adhesion and Risk of Exudative Age-related Macular Degeneration: Paired Eye Study

To evaluate posterior vitreomacular adhesion as a risk factor for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Retrospective, observational case series. We retrospectively reviewed optical coherence tomography (OCT) and fluorescein angiography (FA) of 251 consecutive patients with unilateral exudative AMD. Fellow eyes had no sign of exudative AMD. Vitreomacular adhesion was defined when posterior hyaloid line attached to inner retinal surface was seen in OCT. We compared the incidence of posterior vitreomacular adhesion between the 2 eyes and the association between CNV location and vitreomacular adhesion. We found posterior vitreomacular adhesion in 56 patients (22.3%), and 3 cases in which it was present in both eyes. CNV was mostly present in eyes with vitreomacular adhesion (44/53, 83%), and rarely found in eyes without vitreomacular adhesion (6/53, 11.3%; P = .0007). The location of vitreomacular adhesion was always observed over the area of the CNV in exudative eyes (50/50). Posterior vitreomacular adhesion is associated with CNV in AMD. Chronic vitreomacular traction may be a risk factor for the development of exudative AMD.

Risk Factors for Choroidal Neovascularization and Geographic Atrophy in the Complications of Age-Related Macular Degeneration Prevention Trial

To determine risk factors for choroidal neovascularization (CNV) and of geographic atrophy (GA) in eyes with large drusen. Cohort study within a multicenter, randomized clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. One thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and visual acuity of 20/40 or better in each eye. At baseline, participants provided a brief medical history. Trained readers evaluated baseline color photographs for drusen characteristics and pigmentary abnormalities. One eye of each participant was assigned to laser treatment and the contralateral eye was assigned to observation. The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA from color photographs and fluorescein angiograms obtained during follow-up visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95% confidence intervals (CIs) were obtained from survival analyses of observed and treated eyes, considered separately and combined. Development of CNV and of endpoint GA. Choroidal neovascularization developed in 141 observed eyes and 141 treated eyes, including 57 patients affected bilaterally. Statistically significant risk factors for CNV in the multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for >79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for >or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA developed in 61 observed eyes and in 58 treated eyes, including 29 patients affected bilaterally. Statistically significant risk factors for GA in the multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for >79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95% CI, 2.57-10.1] for >or=25% vs. <10%), retinal pigment epithelium (RPE) depigmentation (RR, 2.64 [95% CI, 1.26-5.53), and focal hyperpigmentation (RR, 10.4 [95% CI, 4.51-24.0] for >or=250 microm vs. none). Among CAPT participants, increased age and focal hyperpigmentation were risk factors for the development of CNV and for GA. Cigarette smoking was significantly associated with CNV only, whereas retinal area covered by drusen and RPE depigmentation were associated significantly with GA only.

Cardiovascular Disease and Hypertension Are Strong Risk Factors for Choroidal Neovascularization

To investigate the association of cardiovascular risk factors and inflammatory markers with neovascular age-related macular degeneration (AMD). Cross-sectional case-control study. Of the 410 of the >/=65-year-old community sample invited to attend, 205 participated (50% response rate). Of the 215 clinic attendees who were invited to participate, 212 agreed to take part (98% response rate). A diagnosis of neovascular AMD in at least one eye was made in 193 clinic attendees and 2 of the community sample. Clinic and community participants underwent a detailed ophthalmic examination with fundus imaging, were interviewed for assessment of putative risk factors, and provided a blood sample. Analysis included levels of serum lipids, intercellular adhesion molecule 1 (ICAM), vascular cellular adhesion molecule (VCAM), and C-reactive protein (CRP). All participants were classified by fundus image grading on the basis of the eye with more severe AMD features. Neovascular AMD. There were 195 participants with choroidal neovascularization in at least one eye, 97 nonneovascular AMD participants, and 115 controls (no drusen or pigmentary irregularities in either eye). In confounder-adjusted logistic regression, a history of cardiovascular disease was strongly associated with neovascular AMD (odds ratio [OR], 7.53; 95% confidence interval [CI], 2.78-20.41). Cigarette smoking (OR, 3.71; 95% CI, 1.25-11.06), being in the highest quartile of body mass index (OR, 3.82; 95% CI, 1.22-12.01), stage 2 hypertension (OR, 3.21; 95% CI, 1.14-8.98), and being in the highest quartile of serum cholesterol (OR, 4.66; 95% CI, 1.35-16.13) were positively associated with neovascular AMD. There was no association between AMD status and serum CRP, ICAM, or VCAM. Our results suggest that cardiovascular disease plays an etiological role in the development of choroidal neovascularization in a proportion of older adults and highlight the importance of control of blood pressure and cholesterol, avoidance of smoking, and maintenance of a normal body weight.

Interleukin-6 Receptor-Mediated Activation of Signal Transducer and Activator of Transcription-3 (STAT3) Promotes Choroidal Neovascularization

Interleukin (IL)-6, a potent proinflammatory cytokine, is suggested to be a risk factor for choroidal neovascularization (CNV) because of its increased levels in the serum of patients with age-related macular degeneration; however, the role of IL-6 in CNV has not been defined. The present study reveals the critical contribution of IL-6 signaling and its downstream STAT3 pathway to the murine model of laser-induced CNV. CNV induction by laser treatment stimulated IL-6 expression in the retinal pigment epithelium-choroid complex, and antibody-based blockade of IL-6 receptor or genetic ablation of IL-6 led to significant suppression of CNV. CNV generation was accompanied by STAT3 activation in choroidal endothelial cells and macrophages, and IL-6 receptor blockade resulted in selectively inhibited phosphorylation of STAT3 but not extracellular signal-regulated kinase 1/2. Consistently, pharmacological blockade of STAT3 pathway also suppressed CNV. In addition, IL-6 receptor neutralization led to significant inhibition of the in vivo and in vitro expression of inflammation-related molecules including monocyte chemotactic protein, intercellular adhesion molecule-1, and vascular endothelial growth factor, and of macrophage infiltration into CNV. These results indicate the significant involvement of IL-6 receptor-mediated activation of STAT3 inflammatory pathway in CNV generation, suggesting the possibility of IL-6 receptor blockade as a therapeutic strategy to suppress CNV associated with age-related macular degeneration.

Vision Loss in Younger Patients: A Review of Choroidal Neovascularization

Choroidal neovascularization (CNV) is a common cause of vision loss in patients <50 years of age. In these patients, CNV is often the result of pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. Rarely, CNV is seen in children, usually in association with inherited macular dystrophies such as Best's disease (vitelliform macular dystrophy) or drusen of the optic nerve. This article discusses the role of optometrists in the detection and management of CNV. Untreated CNV can cause rapid deterioration of central vision and is associated with a poor prognosis. Optometrists may be able to improve the prognosis of younger patients with CNV by recognizing the signs, symptoms, and risk factors for CNV and promptly referring patients with suspected CNV to a retina specialist. They can also help patients by providing long-term support and rehabilitation. Recent treatment advances, such as the availability of verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) therapy, that are applicable to younger patients with CNV have increased the importance of early detection of CNV and prompt referral of patients to a specialist who can treat CNV.

An untreated macular hole with adjacent choroidal neovascularization.

Choroidal neovascularization (CNV) occurs in association with a variety of retinochoroidal disorders. However, it is not normally known to form after an untreated macular hole. A 75-year-old black male presented with a 12-month history of visual loss in his right eye. Funduscopy showed a full-thickness macular hole in the right eye. No treatment was recommended because the decrease in vision appeared to be long standing. Fourteen months later, the patient was noted to have a subretinal hemorrhage superior to the macular hole. Fluorescein angiography revealed an adjacent choroidal neovascular membrane, and focal krypton laser photocoagulation was performed. Recurrent CNV was noted 6 months later, and additional photocoagulation was performed. This case represents the 10th case reported of CNV with a full-thickness macular hole and only the second of a patient with an untreated macular hole and no other risk factors for CNV.

RETICULAR PSEUDODRUSEN

Reticular pseudodrusen refer to a yellow interlacing network 125 microns to 250 microns wide appearing first in the superior outer macula and then extending circumferentially and beyond. Unlike true drusen, they do not fluoresce on fluorescein or indocyanine green angiography, and are best seen in red-free light or with the He-Ne laser of the scanning laser ophthalmoscope. One hundred patients have been seen in our retinal practice with this clinical feature in the past 3 years. All had some manifestation of age-related maculopathy (ARM), and 66% had or subsequently developed subretinal new vessels in one or both eyes. The appearance is attributed to changes in the choroid. Reticular pseudodrusen are an easily recognizable clinical sign, and may be an important risk factor for choroidal neovascularization in ARM.

Hyperopia and Neovascularization in Age-related Macular Degeneration

Refractive errors for phakic eyes of patients referred with age-related macular degeneration were reviewed to determine whether some range of refractive error might be a risk factor for the neovascular form. The authors compared refractive errors of 198 patients with unilateral neovascular disease with refractive errors of 129 patients with bilateral dry disease. These groups had comparable distributions with respect to age, sex, and visual acuity of their better eyes. Student's t tests and multiple linear regression analyses were performed to assess group differences in mean refractive error. Contingency table and multiple logistic regression analyses were performed to determine odds ratios for having the neovascular form based on a stratification of refractive error. By comparing better eyes of the two groups, patients with the unilateral neovascular form had an average spherical equivalent that was 1.0 diopter (D) more hyperopic than that of patients with the bilateral dry form (P < 0.001). Patients with a refractive error of +0.75 D or greater were more likely to have the neovascular form compared with patients with other refractive errors (odds ratio, 2.40; 95% confidence interval, 1.53-3.78; P < 0.001). Similar relationships between the two groups of patients were found by comparing worse eyes. These findings suggest that hyperopia is a risk factor for choroidal neovascularization among patients referred with age-related macular degeneration.

Risk Factors in Age-related Maculopathy Complicated by Choroidal Neovascularization

We evaluated previously reported and hypothesized risk factors for the development of age-related maculopathy (ARM) in a case-control study. We compared 26 patients with documented disciform scarring or choroidal neovascularization with 23 age- and sex-matched controls. Systolic and diastolic blood pressure, smoking history, glucose, lipoprotein profiles, and serum levels of vitamins A, C, and E did not differ significantly between the two groups. Statistically significant associations (P < 0.05) identified by univariate analysis include degree of dermal elastotic degeneration in sun-exposed and sun-protected skin, white blood count, increasing age and small posterior lenticular opacities. Using an interactive multivariate model, only extent of elastosis in sun protected dermis, age and white blood count were predictive (Mult R = 0.652, P < .001). Our data support the concept of a multifactorial etiology of ARM but suggest that generalized increased susceptibility of elastic fibers to photic or other degenerative stimuli is a new and important risk factor for choroidal neovascularization.