History Of Choroidal Neovascularization Research Articles

Inner Choroidal Fibrosis: An Optical Coherence Tomography Biomarker of Severity in Chronic Central Serous Chorioretinopathy

To describe a potential biomarker termed as inner choroidal fibrosis in cases of chronic central serous chorioretinopathy (CSCR) presenting to a tertiary referral center. Observational case series. Five eyes of 4 patients with CSCR were noted to have a gray-white subretinal lesion in the macula, which was analyzed with multimodal imaging. The lesions were hypofluorescent on autofluorescence, fundus fluorescein angiography, and indocyanine angiography. In all cases, a characteristic heterogeneous, hyperreflective lesion in the inner choroid was seen on optical coherence tomography (OCT), corresponding to the white subretinal lesions. The lesion was distinct from the adjacent choroid, with greater reflectivity and greater thickness than the adjacent compressed choroidal vasculature. The dilated outer pachyvessels were pushed outward or sideways in all cases. On OCT-angiography, the corresponding lesion showed flow void areas. We have termed this zone of inner choroidal hyperreflectivity "inner choroidal fibrosis." Upon analyzing the clinical course, 3 of the patients had a history of choroidal neovascularization. The contralateral eye in 2 of these 3 patients also developed choroidal neovascularization. Three of the eyes had an overlying focal choroidal excavation. We report a potential biomarker of CSCR termed "inner choroidal fibrosis" in 4 cases of chronic CSCR. It can best be identified on enhanced depth or swept source OCT as a region of heterogeneous hyperreflectivity in the inner choroid. This fibrosis could be regarded as a degenerative process secondary to more severe disease in the past.

Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621: Phase 1 Dose-Escalation Study Results

To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. Multicenter, open-label, single- and multiple-dose phase 1 study. Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2, best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. All 15 participants completed the 12-week study. There were no serious adverse events, no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.<END ABSTRACT>.

Continued Increase of Axial Length and Its Risk Factors in Adults With High Myopia

Pathologic myopia due to an excessive increase of axial length is associated with severe visual impairments. Systematic analyses to determine the rate of and the risk factors associated with the axial elongation in adults with high myopia based on long-term follow-up of a large population are needed. To determine the risk factors associated with axial elongation in adults with high myopia. This cohort study used the medical records of 43 201 patient visits in a single-hospital database that were collected from January 3, 2011, to December 28, 2018. A total of 15 745 medical records with the patients' sex, best-corrected visual acuity (BCVA), axial length, type of myopic maculopathy, and the presence or absence of choroidal neovascularization (CNV) were reviewed. Data were analyzed from April 3, 2019, to August 5, 2020. Changes in the axial length at each examination were calculated. The significance of the associations between the annual increase of the axial length and age, sex, baseline axial length, types of myopic maculopathy, and a history of CNV was determined. Generalized linear mixed models were used to evaluate the strength of the risk factors associated with an increase of the axial length in high myopia. Among 1877 patients with 9161 visits included in the analysis, the mean (SD) age was 62.10 (12.92) years, and 1357 (72.30%) were women. The mean (SD) axial length was 29.66 (2.20) mm with a mean (SD) growth rate of 0.05 (0.24) mm/y. Among the 9161 visits, 7096 eyes (77.46%) had myopic maculopathy and 2477 eyes (27.04%) had CNV. The odds ratio for inducing a severe elongation of the axial length was 1.46 (95% CI, 1.38-1.55) for female sex, 0.44 (95% CI, 0.35-0.56) to 0.63 (95% CI, 13 0.50-0.78) for older than 40 years, 1.33 (95% CI, 1.15-1.54) for BCVA of less than 20/400, 1.67 (95% CI, 1.54-1.81) to 2.67 (95% CI, 2.46-2.88) for baseline axial length of 28.15 mm or greater, 1.06 (95% CI, 0.96-1.17) to 1.39 (95% CI, 1.24-1.55) for the presence of maculopathy, and 1.37 (95% CI, 1.29-1.47) for prior CNV. This cohort study found continuing axial elongation in adults with high myopia. The risk factors for elongation do not appear to be modifiable, so prevention of myopia may be the best approach to reduce the incidence of pathologic myopia and its complications in the future.

Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration

To understand levels of disease burden and progression in a real-world setting among patients from the United Kingdom with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Retrospective cohort analysis of a multicenter electronic medical record (EMR) database. Patients who were aged ≥50 years with bilateral GA and no history of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites using the EMR. A deidentified data set was constructed from the records held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis, of which 1901 had bilateral GA and form the basis of this report. A sample of records randomly selected from each center was used to validate disease definitions. Progression to blindness (visual acuity [VA] <20 letters or Snellen 3/60 in the better-seeing eye), driving ineligibility (VA ≤70 letters or Snellen 6/12 in the better-seeing eye), progression to CNV, loss of 10 or more letters, and mean change in VA over time. At first record of GA, 7.1% had a VA in the better-seeing eye equal to or lower than the cutoff for blindness registration and 71.1% had a VA that would have rendered them ineligible to drive. Over time, 16% became legally blind (median time to outcome, 6.2 years) and 66.7% became ineligible to drive (median time to outcome, 1.6 years). In the worse-seeing eye, 40.1% lost ≥10 letters in 2.4 years. Among patients with baseline and 24-month VA measurements, mean VA decline was 6.1 letters in the worse-seeing eye (n= 413) and 12.4 letters in the better-seeing eye (n= 414). The rate of progression to CNV in either eye was 7.4% per patient-year. At initial diagnosis, based on VA in the better-seeing eye, a high proportion of patients with bilateral GA were ineligible to drive and approximately 7% were eligible for UK blindness registration. The subsequent reduction in VA that occurred in the better-seeing eye would render a further two-thirds ineligible to drive. These findings emphasize the severity of the visual disability associated with GA secondary to AMD.

Loculation of Fluid in the Posterior Choroid in Eyes With Central Serous Chorioretinopathy

To evaluate potential accumulation of fluid in the outer choroid in eyes with central serous chorioretinopathy. Retrospective observational case series. Patients in 2 community-based retinal practices were evaluated for hyporeflective areas in the outer choroid consistent with collections of fluid using enhanced depth imaging optical coherence tomography. Eligible patients were examined over the preceding 2 years, had a history of central serous chorioretinopathy, and did not have a history of choroidal neovascularization or photodynamic therapy. In the New York group there were 131 eyes of 70 patients who had a mean age of 56.3 (± 12.5) years, and 88 (67.2%) had hyporeflective regions consistent with posterior loculation of fluid in the macular region. In the Minnesota data set there were 91 eyes of 48 patients who had a mean age of 47.9 (± 9.9) years and hyporeflective regions consistent with posterior loculation of fluid was present in 59 (64.8%). In the entire group the mean subfoveal choroidal thickness of those without loculated fluid was 344μm, as compared with 498μm with loculated fluid (P < .001). The areas of loculated fluid were hyporeflective, were larger topographically than the large choroidal vessels, had an angular inner border, and did not have a bounding vascular wall. Posterior loculation of fluid is a common finding in central serous chorioretinopathy, but it has a different pattern and distribution than do collections of fluid in the outer choroid and suprachoroidal space as seen in other forms of choroidal effusion.

MACULAR CHOROIDAL VOLUME VARIATIONS IN HIGHLY MYOPIC EYES WITH MYOPIC TRACTION MACULOPATHY AND CHOROIDAL NEOVASCULARIZATION

To compare the choroidal volume (CV) between emmetropic and highly myopic eyes, and to assess if the presence of myopic fundus abnormalities, myopic traction maculopathy, or choroidal neovascularization affects the CV. We retrospectively reviewed imaging studies of 98 eyes of 98 patients who underwent CV measurement on optical coherence tomography. We included 31 emmetropic eyes (Group 1), 36 highly myopic eyes without vitreoretinal or choroidal pathologies (Group 2), 21 highly myopic eyes with traction maculopathy (Group 3), and 10 highly myopic eyes with history of choroidal neovascularization (Group 3). Eyes with chorioretinal atrophy were excluded. Regression analysis was performed to evaluate the correlation between CV and multiple variables. Choroidal volume was lower in Group 2 than in Group 1 (P < 0.001), and in Groups 3 and 4 than in Group 2 (P < 0.001 and P = 0.002, respectively). Age (P = 0.002), axial length (P < 0.001), sex (P = 0.047), staphyloma (P < 0.001), and myopic group (P = 0.05) were independent predictors for the final CV (R = 0.645). In highly myopic eyes, CV decreased by 0.32 mm for every 10 years and by 0.49 mm per millimeter of axial length. Choroidal thinning is present in highly myopic eyes compared with emmetropic eyes, and is related to age, axial length, sex, and staphyloma. However, myopic eyes with coexisting myopic traction maculopathy or history of choroidal neovascularization have more severe thinning, likely leading to insufficient metabolic supplementation for the macula.

Choroidal Thickness Measurement in Highly Myopic Eyes Using SD-OCT

To measure macular choroidal thickness (CT) using spectral-domain optical coherence tomography (OCT) and to investigate the correlation between CT and age, degree of myopia, and history of macular choroidal neovascularization (CNV). A cross-sectional study included 187 highly myopic eyes of 187 patients examined between January and December 2010. The choroid was imaged with spectral-domain OCT by changing the reference position from the vitreous to the choroid. CT was measured from the outer border of the hyperreflective line corresponding to the retinal pigment epithelium to the inner scleral border. The mean age was 47.21 ± 14.24 years, the mean spherical equivalent refractive error was -13.66 ± 5.77, and the mean subfoveal CT was 100.71 ± 59.98 μm. CT was correlated negatively with age (P < 10(-3)) and refractive error (P < 10(-3)). Forty-two eyes had a history of CNV, the mean CT was 55.45 ± 24.46 μm, and this was significantly thinner than in eyes without CNV (P < 10(-3)). In highly myopic eyes, the choroid is thin and undergoes further attenuation with age and increasing myopia. In addition, these findings suggest that the choroid may play a role in the pathogenesis of CNV.

The Relationship Between Axial Length and Choroidal Thickness in Eyes With High Myopia

To investigate the choroidal thickness in highly myopic eyes with no history of choroidal neovascularization or ocular surgery, and to correlate it with axial length, age, and spherical equivalent. Retrospective, comparative, noninterventional case series. A total of 120 eyes of 83 patients with high myopia (spherical equivalent ≥-6 diopters or axial length ≥26mm) and 96 eyes of 62 healthy patients were studied in a clinical setting. Eyes with prior vitreoretinal surgery or laser or anti-vascular endothelial growth factor therapy were excluded. Eyes were imaged using optical coherence tomography employing a 6-mm line, reference position "Choroid," and image averaging 50. Choroidal thickness was manually measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500-μm intervals up to 2500μm nasal and temporal to the fovea. Statistical analysis was performed. The high myopia group mean age was 54.4 ± 18.2 years (range, 18-99) and mean axial length was 29.17 ± 2.44mm (range, 26.00-35.63). Mean macular choroidal thickness was 115.5 ± 85.3μm (range, 6.9-436.0). The choroid was thickest temporally (134μm), then subfoveally (130μm), and was thinnest in the nasal area (68μm). This pattern differed markedly from the control eyes. In the high myopia group, axial length had the best correlation with choroidal thickness (r= -0.740; P < .001). Choroidal thickness decreased 25.9 ± 2.1μm for each additional millimeter. Axial length is especially associated with choroidal thickness in high myopia. Choroidal thickness profile in highly myopic patients differs from that in emmetropic patients.

Choroidal thickness measurement in highly myopic eyes using SD ‐ OCT

Abstract Purpose to measure macular choroidal thickness (CT) using spectral domain optical coherence tomography (OCT) and to investigate the correlation between CT and age, degree of myopia, and a history of macular choroidal neovascularization (CNV). Methods a cross sectional study was performed in 191 eyes of 106 patients with spherical equivalent (SE) refractive error of 6 diopters (D) or more, between early January 2010 and early June 2010. The choroid was imaged using the spectral domain OCT (OCT TOPCON 2000) by changing the reference position from the vitreous to the choroid without inverting the image. CT was measured from the outer border of the hyperreflective line corresponding to the retinal pigment epithelium (RPE) to the inner scleral border. Results the mean age of the 106 patients was 47,9 years ( ± 14,89 years; range, 18 to 81 years), 32 were men and 74 were women, the mean SE refractive error was 13,73 D (±5,74 D), and the mean subfoveal CT was 100,42 µm (±60,15µm; range, 23‐278). CT was correlated negatively with age (p= 0,01), and refractive error (p=0,01). Fourty eyes had a history of CNV, the mean CT was 52,02 ± 17,65 µm, and this was significantly thinner than the subgroup without CNV (p&lt;0,10‐6 ). Conclusion in highly myopic eyes, the choroid is thin and undergoes further attenuation with increasing age and increasing myopia. In addition, these findings suggest that the choroid may play a role in the pathogenesis of choroidal neovascularization.

Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Highly Myopic Eyes

To measure macular choroidal thickness (CT) in highly myopic eyes using enhanced depth imaging optical coherence tomography (OCT). Retrospective, observational case series. Enhanced depth imaging OCT images were obtained in highly myopic eyes (> or =6 diopters [D]). Images of CT were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. CT was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 1000-mum intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate CT at each location and to correlate CT with age and refractive error. The mean age of the 31 patients (55 eyes) was 59.7 years (+/- 17.6 years; range, 24 to 90 years), and the mean refractive error was -11.9 D (+/- 3.7 D). The mean subfoveal CT was 93.2 microm (+/- 62.5 microm) and was correlated negatively with age (P = .006), refractive error (P < .001), and history of choroidal neovascularization (P = .013). Regression analysis suggested that subfoveal CT decreased by 12.7 mum for each decade of life and by 8.7 microm for each D of myopia. The choroid in highly myopic eyes is very thin and undergoes further thinning with increasing age and degree of myopia. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.

Natural history of choroidal neovascularization after surgical induction in an animal model

To study an expanded time course of surgically induced choroidal neovascularization (CNV) in a porcine model applying fluorescence angiography and immunohistology. Twenty-two porcine eyes underwent vitrectomy, a retinal bleb was raised and the detached retina perforated using endodiathermy. Bruch's membrane was perforated with a retinal perforator at a site where the overlying neuroretina was normal. Eyes were enucleated in a time interval between 30 min and 42 days after the perforation, and the pigs were subsequently killed. Immediately prior to enucleation, fundus photographs and fluorescein angiograms were obtained. Sections of paraffin-embedded eyes were immunohistochemically stained. On fluorescein angiography, membranes aged 14 days or less exhibited leakage in 10/11 cases while the remaining showed persistent staining. The propensity to leak diminished with time and only 1/3 of the oldest membranes leaked. In eyes enucleated immediately after surgery, neuroretinas overlying the induced lesions were intact without apparent atrophy of cells. At day 3, macrophages and myofibroblasts formed membrane-like structures in the subretinal space. At day 7, the outer surface of the membrane was covered by retinal pigment epithelium (RPE) cells and the neuroretinas had suffered damage in the form of outer segment loss. In the time period 14-42 days, the CNV membrane became completely enveloped by RPE cells. The degree of membrane vascularization increased with time and was at its maximum after 42 days. Intact outer segments were identified over the oldest membranes. The formation of surgical CNV membranes followed the normal reparatory pathway and the degree of vascularization of CNV membranes continued to increase during the 42 days. However, propensity to leak diminished with time. We believe that this was because of the fact that RPE cells completely enveloped older membrane and thus prevented leakage from the newly formed vessels. Photoreceptor outer segments, which had atrophied after 7 days, were able to regenerate over CNV membranes and could be identified again after 42 days.

Indocyanine green angiography and transmission defects.

Several reports have suggested that indocyanine green angiography is of value in identifying late hyperfluorescent subretinal tissue presumed to be choroidal neovascularization. However, fluorescein angiography may also reveal late hyperfluorescence from transmission defects caused by atrophy of the retinal pigment epithelium. We studied the indocyanine green angiographic characteristics of transmission defects to determine if indocyanine green angiography can differentiate choroidal neovascularization from the retinal pigment epithelium atrophy. Indocyanine green angiograms of 23 eyes with geographic atrophy secondary to age-related macular degeneration and without any signs or history of choroidal neovascularization were reviewed. Indocyanine green angiography demonstrated late hypofluorescence of various degrees in the area of geographic atrophy. There was no evidence of late hyperfluorescence. Late hyperfluorescence evident on fluorescein angiography which can be caused by choroidal neovascularization or transmission defects is not seen in retinal pigment epithelium atrophy imaged by indocyanine green angiography. According to these results indocyanine green angiography is useful to differentiate occult choroidal neovascularization from areas of retinal pigment epithelium atrophy.

Long term natural history of choroidal neovascularization in pathologic myopia.

Long term natural history of choroidal neovascularization in pathologic myopia.

1322 Long term natural history of choroidal neovascularization in pathologic myopia

1322 Long term natural history of choroidal neovascularization in pathologic myopia