Onset Of Choroidal Neovascularization Research Articles

M2-type macrophage-targeted delivery of IKKβ siRNA induces M2-to-M1 repolarization for CNV gene therapy

Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis.To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase β (IKKβ) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKβ siRNA-loaded liposome (siIKKβ-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKβ-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.

Correlation between AI-measured lacquer cracks extension and development of myopic choroidal neovascularization.

To investigate the correlation between the AI-measured area of the lacquer cracks (LC) at their first detection and the occurrence of a choroidal neovascularization (CNV) during the follow-up in patients affected by pathologic myopia. Secondary outcome was the detection of a correlation between the time to onset of CNV with both baseline LC area and LC area increase during follow-up. Optical coherence tomography (OCT) acquisitions of patients diagnosed with LC were retrospectively analysed. The study population was divided in a CNV group (showing the documented onset of a CNV) and a n-CNV group (no CNV development during follow-up). LC area was measured using MatLab software after the application of a customized method for LC segmentation on infrared (IR) enface images. Forty-five (45) patients with a mean follow-up of 4.9 ± 1.5 years were included. LC area at baseline was 2.82 ± 0.54 mm2 and 1.70 ± 0.49 mm2 in CNV (20 patients) and n-CNV group (25 patients) group respectively (p < 0.001). LC area increase was significantly higher in CNV group (p < 0.001). Time to onset of CNV was linearly correlated with both LC area at baseline (p = 0.006) and LC area increase (p < 0.001). Myopic CNV development is associated with lager LC areas and higher LC area increase during time. Earlier CNV onset is inversely correlated with LC area and LC area increase.

Relationship of Retinal Vessel Caliber with Age-Related Macular Degeneration.

Purpose Evaluate the relationship between retinal vascular caliber and age-related macular degeneration (AMD) severity or progression. Methods A retrospective secondary analysis of 1172 fundus photographs and clinical data from the prospective Age-Related Eye Disease Study (AREDS). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were measured using the Parr–Hubbard–Knudtson formula. Univariate and multivariate regressions were used to determine the association of CRAE, CRVE, and AVR with age, sex, smoking status, presence of cilioretinal artery, and AMD severity at baseline and 5 years using the 9-step AMD severity score. Results Only CRAE and CRVE were higher in men (P < 0.001), current smokers (P < 0.001), and the eyes with a cilioretinal artery (P=0.009 − 0.043). AMD severity was greater in older patients (P=0.001), current smokers (P=0.012), the eyes without a cilioretinal artery (P=0.001), and lower AVR (P=0.034) on multivariate regression but was not influenced by CRAE or CRVE (P=0.240 − 0.500). Choroidal neovascularization (CNV) presence was associated with older age (P=0.003) and absence of a cilioretinal artery (P=0.009), while central geographic atrophy (CGA) was associated with narrower CRAE (P=0.002) and possibly AVR (P=0.046). None of the retinal vessel parameters were predictive of AMD severity score or new onset of CNV or CGA at 5 years. Conclusion A lower arteriole-to-venule ratio may be associated with AMD severity, with narrower arterioles seen in the eyes with geographic atrophy, suggesting a role of the retinal vasculature in AMD pathophysiology. This trial is registered with ClinicalTrials.gov Identifier: NCT00000145.

Clinical course after the onset of choroidal neovascularization in eyes with central serous chorioretinopathy.

Chronic central serous chorioretinopathy (CSC) can be complicated with choroidal neovascularization (CNV); however, the timing of its occurrence and its clinical significance are not well understood. This study aimed to observe the time of choroidal neovascularization detection after CSC diagnosis and determine whether clinical features and prognosis differed in patients with chronic CSC or age-related retinal degeneration.In this retrospective study, medical records of CSC patients complicated with CNV who visited Seoul St. Mary's hospital of Korea between October 2009 and December 2020 were reviewed. The presence of CNV was determined using fluorescein, indocyanine green, or optical coherent tomography angiography (OCTA). Based on the patients’ medical records, we observed the change of clinical pattern, best-corrected visual acuity (BCVA) and central macular thickness (CMT) at CNV detection and at 6 months, 1 year, 3 years, and 5 years following CNV detection.Thirty eyes of 30 patients (male: female ratio of 13:17) were enrolled. Mean age at diagnosis of CSC was 54.0 ± 8.5 years (mean ± standard deviation). On average, CNV was detected 1.65 ± 2.30 years after the diagnosis of CSC. The mean CMT was significantly decreased at 6 months, 1 year, and 3 years after choroidal neovascularization detection (P < .001, P < .001, P = .001 respectively). BCVA tend to improve after CNV detection, but there was no statistical significance at 6 months, 1 year, 3 years, and 5 years (all with P > .05). There were no clinical findings suggesting age-related macular degeneration such as intraretinal, subretinal hemorrhage or drusen in any of the case during follow-up. None of the subjects had severe visual acuity loss of 1.0 logarithm of the minimum angle of resolution (logMAR) (20/200 Snellen equivalent) or greater. Among the subjects, 6 patients (20%) did not require any treatment during observation, while 24 other patients required anti-vascular endothelial growth factor (anti-VEGF) or photodynamic therapy. At the last visit, 22 patients (73.3%) remained stable for more than 6 months, without subretinal fluid recurrence.Choroidal neovascularization was detected earlier than previously reported. There was no rapid deterioration of visual acuity or clinical features even after CNV detection.

Multifocal Evanescent White Dot Syndrome-like Phenotypes Associated with Inflammatory and Myopic Choroidal Neovascularization

ABSTRACT Purpose: To present the observation of multifocal evanescent white dot syndrome (MEWDS)-like phenotypes developing in association with the onset of choroidal neovascularization (CNV) in a series of patients. Methods: Patients presenting to tertiary-care centers with MEWDS-like phenotypes and CNV were identified. Results: Five patients presented for the management of CNV in the context of previous diagnoses of punctate inner choroidopathy (PIC) and/or myopia. In time-periods ranging from 0 days to 12 weeks from the diagnosis of active CNV, MEWDS-like changes were observed. Treatment with anti-VEGF agents were instituted in four cases, in an as-required protocol. 1 patient received systemic steroid. Conclusions: The development of MEWDS-like phenotypes in association with CNVM can occur in eyes with either inflammatory or non-inflammatory CNVM, and in those who were or were not treated with anti-VEGF therapy. The association suggests an inflammatory event, which causes RPE changes and probably induces the development of the CNV.

Silencing fibroblast growth factor 7 inhibits krypton laser-induced choroidal neovascularization in a rat model.

Choroidal neovascularization (CNV), a characteristic of age-related macular degeneration, is an underlying cause of severe vision loss among elderly patients. Fibroblast growth factor (FGF) is suggested to exert an important role in the pathogenesis of CNV. However, the molecular mechanisms governing this event are not fully elucidated. Herein, we identified the potential role of FGF7 in CNV. To examine the roles of FGF7 in the progression of CNV, rat CNV models were established and treated with small interfering RNA (siRNA) against FGF7 or FGF7 overexpression, followed by identification of expression of FGF7 in the CNV modeled rats. Next, proliferation and migration, and in vitro tube formation of human umbilical vein endothelial cells, as well as expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta 2 (TGF-β2) were evaluated. CNV led to upregulated FGF7 expression. Cells in the presence of FGF7 siRNA showed suppressed proliferation, migration, and tube formation, along with downregulated VEGF and TGF-β2 expression. Taken together, functional suppression of FGF7 inhibited the onset of CNV, ultimately highlighting a novel therapeutic target for suppressing CNV progression.

Spectral-domain optical coherence tomography features preceding new-onset neovascular membrane formation

ObjectiveTo determine the frequency and characteristic spectral-domain optical coherence tomography (SD-OCT) features preceding new-onset choroidal neovascularization (CNV) in the fellow eye of neovascular age-related macular degeneration (AMD) with SD-OCT. DesignA prospective, observational study. ParticipantsSixty-eight fellow eyes of patients with unilateral CNV. MethodsSD-OCT was performed at baseline and then monthly. The main outcome measure is the description of retinal morphology 1 month before new onset of neovascularization. ResultsDuring the 48-month observation period, new-onset CNV was observed in 27 fellow eyes. Several morphologic features characterized SD-OCT images ≥1 months before new onset of CNV. These included new retinal pigment epithelium defects (2 eyes), new photoreceptor defects (7 eyes), drusen touching the photoreceptor layer and the external limiting membrane (13 eyes), and new drusen (4 eyes) hyperreflective spots probably representing new growing vessels (5 eyes). ConclusionsMonthly SD-OCT screening of fellow eyes of patients treated with anti–vascular endothelial growth factor enables identification of morphologic changes that may predispose or precede CNV formation. Rapid identification of CNV formation enhances treatment immediacy.

Angiographic and Optical Coherence Tomography Characteristics of Recent Myopic Choroidal Neovascularization

To analyze the contribution of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT) to the diagnosis of recent choroidal neovascularization (CNV) associated with high myopia. Retrospective, observational case series. Ninety eyes of 73 highly myopic patients (refractive error ≥-6 diopters) with CNV in 1 or both eyes were included. Epidemiologic features, refractive error, fundus examination, fluorescein angiography, and SD OCT findings at onset of CNV were analyzed. Mean age at onset of CNV was 54.4 ± 14 years. CNV was bilateral in 17 of 73 cases. Mean refractive error was -13.9 ± 5.2 diopters. Myopic CNV was associated more frequently with patchy or geographic atrophy (P = .019). CNV was associated with exudative features on fluorescein angiography in 82% of cases (64/78), and on SD OCT in 48.6% of cases (36/74). There was no agreement about signs of active CNV between these 2 imaging methods (κ = 25.7 ± 10%; P = .0044). CNV area was significantly smaller in younger patients (<55 years) than in older patients (0.57 mm(2) vs 1.21 mm(2), respectively; P = .023). Exudative features of myopic CNV are more obvious on FA than on SD OCT, suggesting that fluorescein angiography should be performed when new-onset myopic CNV is suspected. Myopic CNV occurring in older patients (≥55 years) is larger than those seen in younger patients and resembles CNV associated with age-related macular degeneration. This suggests an overlap between myopic CNV in older patients and age-related macular degeneration.

Optical coherence tomography changes before the development of choroidal neovascularization in second eyes of patients with bilateral wet macular degeneration

To describe the frequency of neovascular age-related macular degeneration (nAMD) in second eyes of patients undergoing ranibizumab therapy in their first eye and to evaluate the patterns of optical coherence tomography (OCT) abnormalities in fellow eyes before nAMD. Patients who developed choroidal neovascularization (CNV) in the second eye while on treatment for the first eye were identified. OCT scans of the second eyes, performed before the onset of CNV, were retrospectively examined and graded. Frequency of second eye involvement was estimated and patterns of progression of OCT abnormalities were described and classified. In all, 65 out of 749 consecutive patients required ranibizumab in their second eye for treatment-naïve nAMD over a 2-year period. The mean interval from commencement of ranibizumab in first eye to conversion in second eye was 12 months (2-35.5 months). There were three patterns of CNV development: group A (12%, n=8) had no OCT abnormalities in the second eye just before developing CNV; group B (38%, n=25) had no abnormalities at baseline but developed OCT changes more than one visit before conversion and group C (50%, n=32) had OCT changes from baseline, which did not progress until just before conversion. Patients with retinal pigment epithelial elevation without sub-retinal fluid on OCT in their fellow eyes have a high risk of progression to require therapy within a 2-year period. An anticipatory approach may be warranted, but a small group with completely normal OCT appearances can still develop lesions between visits.

Understanding the molecular basis of age-related macular degeneration and how the identification of new mechanisms may aid the development of novel therapies

. Drusen are extracellular deposits con-taining cellular debris and components of the innate immune system, which form between the Bruch’s membrane and the retinal pigment epithelium (RPE). The accumulation of drusen can lead to focal atrophy of the RPE, neurosensory retina and choroid (i.e., dry AMD), and is strongly associated with the onset of choroidal neovascularization, the patho-logical hallmark of wet AMD

Influence of age on visual results of intravitreal bevacizumab for myopic choroidal neovascularization

Abstract Purpose To evaluate the influence of age on the visual and anatomic outcome of myopic patients with choroidal neovascularization (CNV) treated with intravitreal bevacizumab (IVB). Methods Review of retrospectively collected data of 52 eyes in 50 patients with myopic CNV treated with IVB injections (1.25 mg/ 0.05ml). According to the age at onset of CNV, patients were divided into 2 groups: A younger group (&lt; 50 years); (n=25, 27 eyes) and an older group (≥ 50 years); (n=25, 25 eyes). Best corrected visual acuity (BCVA) and central retinal thickness (CRT) measured with optical coherence tomography (OCT) were compared between the two groups over 12 months. Results The mean number of IVB injections was 1.8 in the younger group and 2.0 in the older group. In the younger group, mean BCVA improved from 1.32 logMAR at baseline to 0.77 logMAR at 12 months (p=.002). In the older group, BCVA improved from 1.0 logMAR to 0.84 logMAR at 12 moths (p=.035). There was a mean of 5.1 lines improvement in BCVA from baseline in the younger group versus a mean of 2.2 lines improvement in the older group (p&lt;.05). Decrease in mean CRT was significantly higher in the younger group than in the older one at 12 months: 114.02µm and 68.8µm respectively (p=.003). Conclusion Visual prognosis of myopic CNV treated with IVB seems to be better in patients younger than 50 years.

Clinical Course and Treatment Outcomes of Sorsby Fundus Dystrophy

To analyze the natural history of Sorsby fundus dystrophy and the effect of various treatment methods for choroidal neovascularization (CNV) in this dystrophy. Historical cohort study. A cohort of 42 patients with the Ser181 Cys TIMP3 mutation were identified from the electronic database of genetic retinal diseases in Moorfields Eye Hospital. Retrospective analyses of case records were carried out. Serial best-corrected visual acuity, fundus findings, age at onset of CNV, initial location of CNV, time taken for CNV to progress to subfoveal location, and the interval between development of CNV in the first and second eye were recorded. The time taken for CNV to recur to a subfoveal location in patients in whom argon laser photocoagulation was carried out for extrafoveal CNV also was documented. In cases where photodynamic therapy (PDT) was carried out for subfoveal CNV, the visual outcome, number of PDT treatments, and progression of lesion size were noted. The median age at onset of CNV in the first eye was 46.1 years and in the second eye was 50.3 years. The mean interval between the development of CNV in the first and second eye was 4.5 years. The median age at which vision fell to 20/200 or below was 48 years (first eye) and 54 years (second eye). Argon laser therapy and PDT are not effective in treating CNV of patients with this dystrophy. Antiangiogenic agents may be more effective in this condition. The main cause of blindness resulting from this dystrophy is CNV. Antiangiogenic agents may be useful in preventing visual loss as a result of this condition.

Estimation of visual outcome without treatment in patients with subfoveal choroidal neovascularization in pathologic myopia

To clarify prognostic factors of long-term visual outcome without treatment in patients with myopic choroidal neovascularization (CNV) and estimate a regression equation to predict visual acuity at 5 years after CNV onset. Fifty-four eyes of 54 consecutive patients with high myopia and subfoveal CNV who did not receive treatment were identified using clinical records from 1988 to 2004. Photodynamic therapy not approved for myopic CNV in Japan during this period. The association of best-corrected visual acuity (BCVA) at 5 years after CNV onset with patient age, refractive error, axial length, initial BCVA, myopic retinopathy grade, duration of persistent hemorrhage, CNV size at onset, and size of hemorrhage around the CNV was analyzed using Spearman's correlation and multiple linear regression analysis. BCVA at 5 years after onset was significantly associated with patient age, CNV size, and initial BCVA (P<0.05, Spearman's correlation). The regression equation estimating BCVA at 5 years after CNV onset was based on age and initial BCVA (R2=0.43). When subjects were divided into groups according to age (<40 and >or=40 years), CNV size, axial length and duration of persistent hemorrhage influenced BCVA at 5 years in patients under 40 years; while only initial BCVA was an influence in those at least 40 years old. We developed a linear predictive model to estimate BCVA at 5 years after onset of myopic CNV without treatment based on the identified prognostic factors. This information might be important for managing patients with myopic CNV.

Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration*1

Purpose To investigate the relationship between statin and aspirin use and the risk of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Design Retrospective consecutive case series. Methods All patients 60 years and older with AMD who were seen between January 1, 1990, and March 1, 2003, at the San Francisco Veterans Affairs Hospital Eye Clinic with fundus photographs were included. Patients with other diagnoses predisposing to CNV or incomplete medical records were excluded. The main outcome measure was angiographically evident CNV. Diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables possibly predisposing to CNV or statin use. For patients with CNV, age of onset was recorded; those without CNV were treated as censored. Age-related macular degeneration disease status and time of onset of CNV was compared between patients treated or not treated with statins for at least 6 months. Results Of 326 patients with AMD, 104 had CNV, 204 had dry AMD, and 18 had geographic atrophy (GA). Of CNV subjects, 21 (20%) used statins, compared with 77 (38%) of dry AMD subjects without GA and 6 (33%) of controls with GA (hazard ratio = 0.51, 95% confidence interval (CI) = 0.31–0.86, P = .01). Aspirin use was also significantly associated with decreased rates of CNV; 62 CNV subjects (60%) used aspirin, compared with 154 (75%) dry AMD subjects without GA or 12 (67%) with GA (hazard ratio = 0.63, 95% CI = 0.40–0.98, P = .04). Conclusions Therapy with statins or aspirin is associated with decreased rates of CNV among AMD patients. Additional study with a prospective and/or randomized trial of statin and aspirin use in AMD patients is warranted.

Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration

Purpose To investigate the relationship between statin and aspirin use and the risk of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Design Retrospective consecutive case series. Methods All patients 60 years and older with AMD who were seen between January 1, 1990, and March 1, 2003, at the San Francisco Veterans Affairs Hospital Eye Clinic with fundus photographs were included. Patients with other diagnoses predisposing to CNV or incomplete medical records were excluded. The main outcome measure was angiographically evident CNV. Diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables possibly predisposing to CNV or statin use. For patients with CNV, age of onset was recorded; those without CNV were treated as censored. Age-related macular degeneration disease status and time of onset of CNV was compared between patients treated or not treated with statins for at least 6 months. Results Of 326 patients with AMD, 104 had CNV, 204 had dry AMD, and 18 had geographic atrophy (GA). Of CNV subjects, 21 (20%) used statins, compared with 77 (38%) of dry AMD subjects without GA and 6 (33%) of controls with GA (hazard ratio = 0.51, 95% confidence interval (CI) = 0.31–0.86, P = .01). Aspirin use was also significantly associated with decreased rates of CNV; 62 CNV subjects (60%) used aspirin, compared with 154 (75%) dry AMD subjects without GA or 12 (67%) with GA (hazard ratio = 0.63, 95% CI = 0.40–0.98, P = .04). Conclusions Therapy with statins or aspirin is associated with decreased rates of CNV among AMD patients. Additional study with a prospective and/or randomized trial of statin and aspirin use in AMD patients is warranted.

Factors associated with the development of chorioretinal atrophy around choroidal neovascularization in pathologic myopia.

To examine the influencing factors on the development of chorioretinal atrophy, which is the main cause of long-term visual decrease in myopic choroidal neovascularization (CNV), in a large series of highly myopic patients. Sixty-five patients (81 eyes) with myopic CNV were studied retrospectively. The influence of the patient's age, refractive error, axial length, visual acuity at onset of CNV, size of CNV, and grade of myopic retinopathy on the extent of chorioretinal atrophy more than 3 years after CNV onset was investigated by means of multiple linear regression analysis. Seventy-seven of 81 eyes (95.1%) developed chorioretinal atrophy around myopic CNV during the follow-up period. Multiple linear regression revealed that age was the most influencing factor for the development of chorioretinal atrophy in all the subjects. When we divided the subjects into two groups according to their age, however, CNV size was the only factor to influence the development of chorioretinal atrophy in the patients younger than 40 years, whereas age was still the only influencing factor in those older than 40 years. The factors influencing the development of chorioretinal atrophy differ according to patient age. Local factors, such as CNV size, determine the tendency to develop chorioretinal atrophy in young patients. Systemic factors, such as patient age, play a greater part in older subjects.

Myopic choroidal neovascularization: A 10-year follow-up

Purpose To clarify the long-term visual outcome of choroidal neovascularization (CNV) in eyes with high myopia in Asian patients. Design We reviewed the medical records of 25 consecutive patients (27 eyes) with myopic CNV who were followed up for at least 10 years after the onset of CNV. Visual acuity was examined 10 years after CNV onset. Intervention Demographic and clinical data were obtained from the patients’ medical records. Main outcome measures Visual acuity readings during the 10 years after CNV onset. Results At the onset of CNV, 19 eyes (70.4%) had a visual acuity better than 20/200, and six eyes (22.2%) had a visual acuity better than 20/40. Three years after the onset of CNV, 15 eyes (55.5%) retained a visual acuity of better than 20/200. At 5 and 10 years after the onset, however, visual acuity dropped to 20/200 or less in 24 eyes (88.9%) and in 26 eyes (96.3%), respectively. The logarithm of the minimum angle of resolution (logMAR) visual acuity was significantly worse at 5 and 10 years after onset as compared with that at CNV onset. Chorioretinal atrophy developed around the regressed CNV in 26 eyes (96.3%) at 5 and 10 years after the onset of CNV. Conclusions Long-term visual outcome of myopic CNV is extremely poor. The visual acuity of almost all of the patients dropped to 20/200 or less within 5 to 10 years after the onset of CNV, secondary to the development of chorioretinal atrophy around the regressed CNV. These findings indicate that active treatments should be recommended to prevent long-term visual impairment in Asian patients with myopic CNV.

Long-term visual prognosis of choroidal neovascularization in high myopia: A comparison between age groups

ObjectiveTo analyze visual outcome in highly myopic patients of different age groups with choroidal neovascularization (CNV). DesignRetrospective observational case series. ParticipantsWe reviewed the medical records of 63 consecutive patients (73 eyes) with myopic CNV. The patient population was divided into two groups according to age at onset of CNV (≤40 and >40 years old). InterventionDemographic and clinical data were obtained from the patients’ medical records. Main outcome measuresVisual acuity at least 3 years after CNV diagnosis. ResultsGroup 1 (≤40 years old) consisted of 22 patients (26 eyes), and group 2 (>40 years old) consisted of 41 patients (47 eyes). Throughout the follow-up period, group 1 retained better visual acuity than group 2. Almost half the patients in group 1 retained a final visual acuity better than 20/40. No significant change occurred in the logarithm of the minimum angle of resolution (logMAR) in group 1 during follow-up. Group 2 had worse visual acuity at the initial evaluation than did group 1, and a statistically significant worsening of logMAR was found during the follow-up period. More than half of the patients in group 2 had a final visual acuity less than 20/200. In addition, group 2 had a larger area of CNV, and chorioretinal atrophy was more frequently seen after the regression of CNV than in group 1. ConclusionsThe visual prognosis of myopic CNV is influenced by age at onset. The results of this study indicate that patient age at the time of onset of myopic CNV should be considered when determining the therapeutic course.

Choroidal neovascularization in the choroidal neovascularization prevention trial

Objective This study aimed to describe characteristics of choroidal neovascularization (CNV) that developed in high-risk eyes of patients with age-related macular degeneration (AMD) enrolled in the Choroidal Neovascularization Prevention Trial (CNVPT). Design Consecutive case series among patients enrolled in a multicenter, randomized controlled trial. Participants Eighteen eyes of 18 patients who developed exudative AMD were studied from among 156 patients with large drusen enrolled in the Bilateral Drusen Study and 120 patients having one eye with exudative AMD and the other eye with large drusen enrolled in the Fellow Eye Study. The CNVPT Fellow Eye Study provided 12 eyes (10, treatment group; 2, control group), and the CNVPT Bilateral Drusen Study contributed 6 eyes (4, treatment group; 2, control group). Methods The CNVPT Reading Center assessment and grading of patients with CNV and other exudative complications was reviewed. Main outcome measures Onset of CNV, laser intensity for treated eyes, classification of lesion components, size of lesion, location of lesion, foveal involvement, and change in visual acuity were measured. Results Eighteen eyes showed onset of CNV between 2 and 21 months after enrollment. In comparison with the CNVPT Laser Standard Intensity, variations in laser treatment intensity (6 eyes graded less than standard intensity and 8 eyes graded standard intensity) were not associated with CNV events. Seventeen of 18 eyes showed occult CNV in whole or in part, and only 1 eye manifested purely classic CNV. The median size range was 2 to 3.5 disc areas. Among the 14 treated eyes that developed exudative lesions, 7 showed subfoveal involvement and 13 had CNV associated with the region of treatment. At the time of the CNV event, 9 of 18 eyes showed greater than a 2-line loss of vision from baseline while the remaining eyes were stable. Conclusions Preliminary data show that visually significant exudative manifestations of AMD may develop in patients with high-risk drusen who undergo macular laser photocoagulation. The CNV lesions typically are occult, often subfoveal, and associated with the region of treatment. Longer follow-up is warranted.