Algorithm of the major and minor diagnostic criteria for active myopic choroidal neovascularization.

PURPOSE: To propose an algorithm of the major and minor diagnostic criteria for macular myopic choroidal neovascularization (mCNV). METHODS: This single-center, retrospective, cross-sectional study was based in Istituto Auxologico Italiano, Milan, Italy. Two authors evaluated the clinical and imaging parameters of eyes with high myopia (spherical equivalent of -6D or less) and suspected to have naïve, recurrent, or inactive mCNV. Recordings of the eyes that met the inclusion criteria were then independently evaluated by two other senior retinal specialists. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and OCT angiography were used for multimodal imaging. RESULTS: One-hundred and twenty-two eyes (n = 107; 39 men, 68 women) were included in the study. The mean patient age was 66 years (range, 22-89 years). There were 83 and 39 eyes in the active mCNV and control groups, respectively. The best diagnostic algorithm had positive- and negative-predictive values of 89% and 85%, respectively, and was based on four criteria: leakage/staining on FA, retinal thickening, fuzzy area on SD-OCT, and recent metamorphopsia. When excluding FA-derived findings, retinal pigment epithelium (RPE) features played a diagnostic role in 33 eyes (27%). Twenty-seven eyes with active mCNV (32%) did not have the fuzzy area. Taken singularly, no clinical or imaging parameter had both sensitivity and specificity greater than 78%. Matching of 2 or 3 biomarkers did not yield a sensitivity or specificity greater than 79%. Sensitivities and specificities ≥ 90% were found in ten criteria combinations that included four to five biomarkers. The most frequent were metamorphopsia, fuzzy area, retinal thickening, and leakage. Less frequently, they included hemorrhage, staining, and RPE features such as elevation, flattening, and focal interruption. For all the parameters, the agreement between the investigators was good (Cohen k ≥ 0.66), being the lowest when detecting the ELM interruption within the lesion. CONCLUSIONS: A combination of at least four clinical and biological markers yielded the highest positive- and negative-predictive values. More ("major") and less ("minor") frequent diagnostic criteria are proposed.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS AFTER MYOPIC NEOVASCULARIZATION.

PURPOSE: To describe the optical coherence tomography (OCT) angiography features of subretinal fibrosis in eyes with myopic choroidal neovascularization after natural evolution or secondary to intravitreal anti-vascular endothelial growth factor therapy. METHODS: Retrospective observational case series. All eyes underwent a multimodal imaging examination including fluorescein angiography, spectral domain OCT, OCT angiography, and en face OCT. RESULTS: Twenty-five eyes of 25 patients with mean age of 56.4 ± 14.9 were included in the study. Subretinal fibrosis was diagnosed at mean 30 (range 6-116) months before inclusion. Within the subretinal fibrosis, an abnormal vascular network was observed in 20/25 (80%) eyes, located typically in the outer retina (18/20, 90%) or the choriocapillaris (14/20, 70%) segmentation. The most prevalent patterns were "round tangle" and "tapered tangle." On en face OCT, the subretinal fibrosis was evidenced in 24/25 (96%) eyes, most prevalently in the outer retina (21/25, 84%) and in the choriocapillaris (18/25, 72%), where main feature was white-hyperreflective (20/21, 95%) and dark-hyporeflective (17/18, 94%) appearance, respectively. The presence of subretinal fibrosis on en face OCT was positively correlated with the presence of abnormal vascular network on OCT angiography in 61% of the cases (P = 0.005). CONCLUSION: Subretinal fibrosis secondary to myopic choroidal neovascularization frequently contains blood flow within a persistent abnormal vascular network as assessed by OCT angiography.

Increased soluble urokinase plasminogen activator receptor (suPAR) levels in neovascular age-related macular degeneration: a role for inflammation in the pathogenesis of the disease?

PURPOSE: To evaluate the plasma concentration of the soluble form of the urokinase-type plasminogen activator receptor ((s)uPAR), an established biomarker of chronic inflammation, in patients affected by neovascular age-related macular degeneration. METHODS: Forty consecutive patients affected by age-related macular degeneration and 52 subjects with no history of the disease were included in this case-control study. The two groups of individuals considered for the study were matched for age, sex, and class of medications taken. Plasma concentration of suPAR was measured using a specific ELISA assay (suPARnostic, Birkeroed, Denmark). RESULTS: The case and control groups were similar for age, gender distribution, weight, height, and systolic and diastolic blood pressure, as well as for dyslipidemia and high blood pressure medication (P > 0.28). The plasma concentrations of suPAR were significantly increased in patients with neovascular age-related macular degeneration when compared to controls (6.19 ± 2.2 ng/ml, vs 5.21 ± 1.5, respectively, mean ± SD P = 0.01). CONCLUSIONS: Patients with neovascular age-related macular degeneration display increased plasma levels of suPAR, suggesting that chronic inflammation may be involved in the pathogenesis of the disease.

Endothelial progenitor cells and response to ranibizumab in age-related macular degeneration.

BACKGROUND: Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV. METHODS: The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab. RESULTS: When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell-derived factor 1, but not of monocytic EPCs. CONCLUSION: The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell-derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.

Inflammation and macular oedema after pars plana vitrectomy.

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches.

Vascularized retinal pigment epithelial detachment in age-related macular degeneration: treatment and RPE tear incidence.

BACKGROUND: To review vascularized-pigment epithelial detachment (V-PED) treatment visual outcome, and to assess acute retinal pigment epithelium (RPE) tear incidence. METHODS: One hundred and thirty-two eyes of 125 consecutive patients with age-related macular degeneration and V-PED were included. Ninety-four eyes (71.2%) were associated with choroidal new vessels (CNV), 38 (28.8%) with retinal angiomatous proliferation (RAP). Patients, treated over a 10-year period with the time-current therapy, received: verteporfin photodynamic therapy (PDT) (group 1, 38 eyes), combined intravitreal triamcinolone acetonide (IVTA) and PDT (group 2, 44 eyes) or intravitreal anti-VEGF injection (bevacizumab or ranibizumab) (group 3, 50 eyes). RESULTS: Mean follow-up was 20.5 months. At month 12, all eyes treated with PDT or with IVTA and PDT showed a mean significant severe visual decrease. Eyes with CNV lost -0.67 and -0.37 logMAR (p < 0.01 and p < 0.01 respectively), and eyes with RAP -0.55 and -0.31 logMAR (p < 0.01 and p = 0.01 respectively). RPE tear occurred in 14 eyes (36.8%) and in six eyes (13.6%) in groups 1 and 2 respectively. Eyes treated with anti-VEGF therapy showed slight mean visual acuity decrease at month 12. Those with CNV had a mean baseline best-corrected visual acuity (BCVA) of 0.36 ± 0.24 logMAR, final of 0.44 ± 0.30 logMAR (-0.08 logMAR, n.s.). In eyes with RAP, mean baseline BCVA was 0.58 ± 0.39 logMAR, final was 0.78 ± 0.47 logMAR (-0.20 logMAR, n.s.). RPE tear occurred in 14 eyes (36.8%). Patients with either V-PED with CNV or a better baseline BCVA showed greater risk of acute RPE tear (p = 0.01 and p = 0.003 respectively). CONCLUSIONS: Effective treatment for vascularized PED is still lacking. Until now, only stabilization of the disease has been achieved using anti-VEGF therapy, but the risk of RPE tear can further hamper our expectations. Baseline characteristics are helpful for prognosis, but patients must be informed of the uncertain response. New therapeutic strategies are needed.

Intravitreal bevacizumab for nonsubfoveal choroidal neovascularization associated with angioid streaks.

PURPOSE: To evaluate the effects of intravitreal bevacizumab injections in the treatment of nonsubfoveal choroidal neovascularization (CNV) associated with angioid streaks. DESIGN: Nonrandomized, interventional, prospective case series. METHODS: Fifteen patients (15 eyes) affected by juxtafoveal or extrafoveal CNV secondary to angioid streaks were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) chart, optical coherence tomography (OCT), and fluorescein angiography (FA). The protocol treatment included a first injection, followed by repeated injections over a 12-month follow-up period on the basis of the detection of new hemorrhage on biomicroscopic examination, any type of fluid on OCT, or presence of leakage on FA. PRIMARY OUTCOME MEASURES: Mean changes in BCVA and proportion of eyes gaining at least 10 letters (2 ETDRS lines) at the end of the follow-up. SECONDARY OUTCOMES: Mean changes of central macular thickness (CMT) and extension to the fovea. RESULTS: Mean BCVA did not change throughout the follow-up period, being 0.2 ± 0.2 logMAR at baseline and 0.2 ± 0.3 logMAR at the 12-month examination. A functional improvement of at least 2 ETDRS lines was achieved by 5 eyes (33%), with 3 eyes (20%) gaining 3 lines. Mean CMT at baseline was 215 ± 13 µm and 225 ± 85 µm at the 12-month examination. Two eyes (13.3%) showed CNV extension to the fovea. CONCLUSIONS: Intravitreal bevacizumab injection can be a beneficial approach for the management of nonsubfoveal CNV secondary to angioid streaks over a 1-year follow-up.

SD-OCT patterns of the different stages of choroidal metastases.

A diagnosis of choroidal metastasis is based on the patient's clinical history, the tumor's ophthalmoscopic appearance, and instrumental imaging results such as ultrasonography, fluorescein angiography, fundus autofluorescence, indocyanine green angiography, and optical coherence tomography. Spectral-domain optical coherence tomography (SD-OCT) has provided additional useful information for clinical diagnosis: a pattern of hyperintense irregular spots in the context of the photoreceptor layer and in the retinal pigment epithelium, subretinal fluid, and marked irregularity of the retinal pigment epithelium with thickening and gross undulation. The authors describe a case of bilateral choroidal metastasis presenting peculiar SD-OCT features acquired at different stages. They emphasize the central role of SD-OCT among instrumental imaging procedures and for final successful diagnosis.

Intravitreal bevacizumab for a subfoveal myopic choroidal neovascularization in the first trimester of pregnancy.

PURPOSE: To report the clinical course of a highly myopic woman treated by a single intravitreal injection of bevacizumab during the first trimester of pregnancy. METHODS: Observational case report. A 35-year-old woman affected by pathologic myopia complained of blurred vision in her left eye in the fourth week of pregnancy. A subfoveal myopic choroidal neovascularization (CNV) was diagnosed on the basis of slit-lamp fundus biomicroscopy and fluorescein angiography. After discussing the treatment-related risks, she was administered an intravitreal injection of bevacizumab in her seventh gestational week. During pregnancy, fetal ultrasound and ophthalmic examination were performed monthly. After delivery, the mother and infant were followed quarterly for 12 months. RESULTS: The patient had an uneventful prenatal course and delivered a healthy full-term infant. Significant visual improvement with no documented adverse events related to treatment was obtained. CONCLUSIONS: In our experience, a single intravitreal bevacizumab injection administered during the first trimester of pregnancy did not provoke any complications, and was effective in myopic CNV treatment. Further studies are warranted to provide more detailed information about this treatment and the related risks in pregnant women.

Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa treated with intravitreal bevacizumab.

PURPOSE: To describe a case of juxtafoveal choroidal neovascularization (CNV) occurring in a patient affected by retinitis pigmentosa (RP), treated with intravitreal bevacizumab over a 12-month follow-up. METHODS: A 66 year-old woman referred to our center for visual acuity deterioration was diagnosed as having classic juxtafoveal CNV associated with RP. The patient was treated with intravitreal bevacizumab, and was regularly monitored every month. RESULTS: At the end of the 12-month follow-up, best corrected visual acuity changed from 20/200 to 20/100 in the affected eye. Five intravitreal bevacizumab injections were required to obtain the stabilization of the CNV. CONCLUSIONS: Intravitreal bevacizumab is effective in producing juxtafoveal CNV stabilization and visual acuity improvement in a patient affected by RP, over a 12-month follow-up. Future studies are required to ascertain the best therapeutic approach for CNV complicating RP.

Elevated erythropoietin and vascular endothelial growth factor levels in an adolescent with retinal neovascularization from a chronic rhegmatogenous retinal detachment.

PURPOSE: To evaluate the role of erythropoietin and vascular endothelial growth factor (VEGF) in a patient with retinal neovascularization from a rhegmatogenous retinal detachment of long duration. METHODS: Fundus photography, fluorescein angiography, and vitreous analysis were performed. The vitreous concentrations of erythropoietin and VEGF were measured by enzyme-linked immunosorbent assays and compared with control levels. RESULTS: An adolescent with a history of mild retinopathy of prematurity presented with a retinal detachment found by routine examination. The patient had a rhegmatogenous retinal detachment with signs of chronicity and extensive retinal neovascularization. The patient's erythropoietin level was higher than those of patients with proliferative diabetic retinopathy. The patient's VEGF level was not as high as those of patients with proliferative diabetic retinopathy but was elevated compared with those of patients without neovascularization. CONCLUSION: Vitreous concentrations of erythropoietin and VEGF can be elevated in patients with neovascularization secondary to a rhegmatogenous retinal detachment of long duration.