Sub-retinal Pigment Epithelium Fluid Research Articles

Is Spectral-Domain Optical Coherence Tomography Essential for Flexible Treatment Regimens with Ranibizumab for Neovascular Age-Related Macular Degeneration?

Purpose. To evaluate the ability of spectral-domain optical coherence tomography to detect subtle amounts of retinal fluid when the choroidal neovascularization is detected as inactive via time-domain optical coherence tomography and clinical examination in neovascular age-related macular degeneration (nAMD) patients. Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment were included in this cross-sectional, prospective study. All patients were imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab injection. The presence of subretinal, intraretinal, and subretinal pigment epithelium fluid (subRPE) in SD-OCT was evaluated; also mean central retinal thickness (CRT) and the rate of vitreoretinal surface disorders detected via the two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1 ± 51.3 and 325.7 ± 78.8 microns. Sixteen patients (32.6%) showed any kind of retinal fluid via SD-OCT. In detail, 8 patients (16.3%) showed subretinal fluid, 10 patients (20.4%) showed intraretinal fluid, and 3 patients (6.1%) showed SubRPE fluid. The ability of detecting vitreoretinal surface disorders was comparable between the two devices, except vitreomacular traction. Conclusion. SD-OCT is essential for the nAMD patients who are on an as-needed treatment regimen with ranibizumab. Only TD-OCT and clinical examination may cause insufficient treatment in this group of patients.

Super-dose Anti-VEGF (SAVE) Trial: 2.0 mg Intravitreal Ranibizumab for Recalcitrant Neovascular Macular Degeneration–Primary End Point

To determine whether a higher dose of intravitreal ranibizumab could improve the anatomy and best-corrected visual acuity (BCVA) in eyes with neovascular age-related macular degeneration (AMD) with persistent disease activity despite monthly intravitreal anti-vascular endothelial growth factor (VEGF) injections. Phase I to II multicenter, open-label, controlled clinical trial. Eighty-seven patients with recalcitrant neovascular AMD, defined as having leakage on fundus fluorescein angiography or spectral domain optical coherence tomography (SD-OCT) despite monthly anti-VEGF injections. Patients were treated with 2.0-mg ranibizumab injections monthly for 3 doses and monitored with Early Treatment Diabetic Retinopathy Study (ETDRS) 4-m refractions, clinical examinations, and SD-OCT. The mean change in baseline visual acuity (VA), the percentage of patients who experienced a loss or gain of 15 or more letters in ETDRS BCVA, the mean change in central retinal thickness, and the incidence of adverse events. Eighty-seven patients with an average of 24 injections before enrollment and a mean of 10.4 injections in the preceding 12 months had a mean refracted VA of 69.2 ETDRS letters (20/41 Snellen) and a mean central subfield of 422 μm at baseline. Mean VA gain over baseline was +2.5 letters at day 7 (n = 82), +3.7 letters at month 1 (n = 87), +3.9 letters at month 2 (n = 87), and +3.3 letters at month 3 (20/36 Snellen; P = 0.001; n = 86). Anatomic outcomes showed a mean optical coherence tomography central subfield thickness improvement from baseline of -48.4 μm at day 7 (n = 84), -37.5 μm at month 1 (n = 87), -42.4 μm at month 2 (n = 85), and -33.1 μm at month 3 (P = 0.01; n = 86). Intravitreal injections of 2.0 mg ranibizumab led to statistically significant VA gains and anatomic improvement in patients with persistent intraretinal, subretinal, or subretinal pigment epithelial fluid during a previous regimen of chronic monthly 0.5-mg ranibizumab injections.

Prognostic factors for visual outcome after intravitreal bevacizumab injection for pigment epithelial detachment in AMD

AbstractPurpose To evaluate the prognostic factors for visual outcome after intravitreal bevacizumab injection in patients with pigment epithelial detachment (PED) in AMDMethods Thirty eyes in 30 patients with CNV and PED in AMD who had received intravitreal bevacizumab injections were retrospectively reviewed. Initial visual acuity, pigment epithelial detachment size, retinal or subretinal fluid resolution and CNV location were evaluated at 12 months.Results Initial visual acuity was not correlated with BCVA at 12 months (p=0.063). CNV at the edge of PED appears to respond more favorably at 12 months (p=0.033) than CNV within PED. Sub and intraretinal fluid initially resolved faster than the sub‐PED fluid (P = 0.041).The subretinal pigment epithelial fluid was highly resistant. Sub and intraretinal fluid response did not appear to be related to PED size. Visual acuity improvement was similar in both groups: large and minimal PED component.Conclusion The location of CNV and the retinal or subretinal fluid resolution were the main prognostic factors for visual outcome. Bevacizumab was very effective in reducing more of the sub‐ and intraretinal fluid than the PED fluid in AMD with CNV.

PILOT STUDY FOR THE DETECTION OF EARLY EXUDATIVE AGE-RELATED MACULAR DEGENERATION WITH OPTICAL COHERENCE TOMOGRAPHY

Optical coherence tomography (OCT) provides microscopic retinal images. Optical coherence tomography is noninvasive, using light waves to produce detailed retinal images. Here, we investigate the ability of OCT to detect early choroidal neovascularization in age-related macular degeneration. Seventy-nine patients, diagnosed with nonexudative macular degeneration in one eye and exudative macular degeneration in the other were enrolled in this prospective, observational, nonrandomized study. Participants underwent examination (visual acuity, intraocular pressure, biomicroscopy, and ophthalmoscopy) followed by OCT in the study eye (nonexudative macular degeneration eye) every 3 months for 2 years. If examination did not show choroidal neovascularization, but OCT images raised suspicion, patients were reexamined in 4 weeks to 6 weeks and/or fluorescein angiography was performed. Visual acuity, OCT anomaly detected, and time between OCT and fluorescein angiography detection were examined. Fifteen (19%) patients developed exudative macular degeneration, as confirmed by fluorescein angiography, in the study eye. Four additional patients showed potential exudative macular degeneration on OCT only. Of the 15 patients who developed exudative macular degeneration, 13 had disease progression identified on OCT before examination and/or fluorescein angiography showed changes. Subretinal pigment epithelium fluid was the most common OCT anomaly, with development of sub-/intraretinal fluid also visible. Optical coherence tomography could be a powerful screening tool for patients with age-related macular degeneration at high risk for developing choroidal neovascularization.

PROGNOSTI IMPLICATIONS OF PIGMENT EPITHELIAL DETACHMENT IN BEVACIZUMAB (AVASTIN)-TREATED EYES WITH AGE-RELATED MACULAR DEGENERATION AND CHOROIDAL NEOVASCULARIZATION

To evaluate the response to primary bevacizumab treatment of eyes with age-related macular degeneration (AMD) and choroidal neovascularization (CNV) with a large pigment epithelial detachment (PED) component and to compare the increase in visual acuity and reabsorption of retinal fluid in PED eyes with eyes with CNV in AMD with a minimal to no PED component. We reviewed 43 consecutive eyes with CNV and AMD on primary bevacizumab therapy. There were 13 eyes with a large PED component in AMD with CNV and 30 eyes with a minimal to no PED in CNV. Only patients with no previous treatment for AMD and those started on purely intravitreal bevacizumab treatment were taken in the study. Pigment epithelial detachment size, time to PED collapse, and retinal or subretinal fluid resolution were determined as was Early Treatment Diabetic Retinopathy Study vision. Time to resolution of intraretinal and subretinal fluid was compared between the PED group and the non-PED group using survival analysis. In AMD with CNV eyes having a large PED component, sub- and intraretinal fluid initially resolved faster than the sub-PED fluid (P = 0.03). The subretinal pigment epithelial fluid itself was highly resistant. Visual acuity improvement was similar in both groups. Despite monthly intravitreal bevacizumab injections for neovascular AMD patients with a large component PED, the majority had minimal to no response of the PED. Sub- and intraretinal fluid response was faster in neovascular AMD without large PEDs, but after 7 months, vision change and reabsorption of intra- and subretinal fluid were similar in the two groups. Sub- and intraretinal fluid response did not appear to be related to PED size. Bevacizumab was very effective in reducing more of the sub- and intraretinal fluid than the PED fluid in AMD with CNV.

The Role of Spectral-Domain OCT in the Diagnosis and Management of Neovascular Age-Related Macular Degeneration

Spectral-domain optical coherence tomography (SD-OCT) has emerged as the ancillary examination of choice to assist the diagnosis and management of neovascular age-related macular degeneration (AMD). SD-OCT provides more detailed images of intraretinal, subretinal, and subretinal pigment epithelium fluid when compared to time-domain technology, leading to higher and earlier detection rates of neovascular AMD activity. Improvements in image analysis and acquisition speed make it important for decision-making in the diagnosis and treatment of this disease. However, this new technology needs to be validated for its role in the improvement of visual outcomes in the context of anti-angiogenic therapy.

Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years

The combination of verteporfin photodynamic therapy (PDT) and anti-angiogenics has been shown to be safe and efficacious in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of this study is to demonstrate long-term prevention of vision loss and improvement in best-corrected visual acuity (BCVA) after treatment with one-time reduced-fluence-rate PDT followed by administration of ranibizumab on a variable dosing regimen over 24 months in patients with neovascular AMD. Secondary outcome measures included the change in central macular thickness (CMT), reinjection frequency, and safety. This prospective, nonrandomized, open-label, single-center study enrolled 27 consecutive patients (27 eyes) presenting at the Leuven University Eye Hospital with previously untreated, active neovascular AMD between September 2006 and January 2007. All patients were treated with one-time, reduced-fluence-rate verteporfin PDT, followed by intravitreal ranibizumab 0.5 mg on the same day. A second and third ranibizumab injection were given at weeks 4 and 8, respectively, after which patients were followed up monthly for 24 months. Additional treatment with ranibizumab was administered to eyes with active neovascularization as indicated clinically and on imaging studies. Retreatment was based on the following criteria: (1) presence of subretinal fluid (SRF), intraretinal edema or sub-retinal pigment epithelial fluid, as seen on OCT; (2) increase of CMT by >100 mm on OCT; (3) signs of active CNV leakage on fluorescein angiography; (4) new sub- or intraretinal hemorrhage; and (5) BCVA decreased of > or =5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. If any single criterion for reinjection was fulfilled, retreatment with ranibizumab was administered. Twenty-five patients completed the 2-year study. Occult CNV was present in 64% and retinal angiomatous proliferative (RAP) lesions were present in 24% of the study eyes. The remaining three eyes had lesions classified as classic (one eye) or predominantly classic (two eyes) CNV. Month 24 data are available for 25 eyes (25 patients; age 55-86 years; mean 77; standard deviation (SD) = 7.2). Mean baseline VA was 58.6 letters (range: 35-70; SD = 8.4); 24-month VA was 66.2 letters (35-82; 12.7), not including one warfarin-treated patient who suffered vitreous hemorrhage. The mean visual acuity improved by 7.2 letters (p < 0.05) and the mean CMT decreased by 146 mum. VA improved >3 lines (15 letters) in 16%; improved 1-3 lines in 20%; remained within one line of baseline in 32%, decreased 1-3 lines in 16%, and decreased >3 lines in 16%. Losses of >3 lines were due to vitreous hemorrhage, geographic atrophy, fibrosis, and growth of an initially small CNV lesion. An average of 5.1 injections (range: 3-9) were administered during the first 12 months, and 7.1 injections (3-13) over 24 months. A total of 178 injections were performed; no systemic side-effects, uveitis, or choroidal collateral vascular damage were observed. Two patients were lost to follow-up. Combined PDT and ranibizumab injection the same day was well tolerated in all patients. Eighty-four percent of patients had stable or improved vision at month 24.

Quantification of Error in Optical Coherence Tomography Central Macular Thickness Measurement in Wet Age-related Macular Degeneration

To assess error indicators encountered during optical coherence tomography (OCT) automated retinal thickness measurement (RTM) in neovascular age-related macular degeneration (NVAMD) before and after bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) treatment. Retrospective observational cross-sectional study. Each of the 6 radial lines of a single Stratus fast macular OCT study before and 3 months following initiation of treatment in 46 eyes with NVAMD, for a total of 552 scans, was evaluated. Error frequency was analyzed relative to the presence of intraretinal, subretinal (SR), and subretinal pigment epithelial (SRPE) fluid. In scans with edge detection kernel (EDK) misplacement, manual caliper measurement of the central macular (CMT) and central foveal (CFT) thicknesses was performed and compared to the software-generated values. The frequency of the various types of error indicators, the risk factors for error, and the magnitude of automated RTM error were analyzed. Error indicators were found in 91.3% and 71.7% of eyes before and after treatment, respectively (P = .013). Suboptimal signal strength was the most common error indicator. EDK misplacement was the second most common type of error prior to treatment and the least common after treatment (P = .005). Eyes with SR or SRPE fluid were at the highest risk for error, particularly EDK misplacement (P = .039). There was a strong association between the software-generated and caliper-generated CMT and CFT measurements. The software overestimated measurements by up to 32% and underestimated them by up to 15% in the presence of SR and SRPE fluid, respectively. OCT errors are very frequent in NVAMD. SRF is associated with the highest risk and magnitude of error in automated CMT and CFT measurements. Manually adjusted measurements may be more reliable in such eyes.

Fundus Autofluorescence Imaging in Serous and Drusenoid Pigment Epithelial Detachments Associated With Age-Related Macular Degeneration

To investigate the fundus autofluorescence (FAF) imaging findings in patients with serous and drusenoid pigment epithelial detachment (PED) associated with age-related macular degeneration (AMD). Observational case series. Fourteen eyes of 13 consecutive patients with serous (n = 10) and drusenoid (n = 4) PED were prospectively included. In all cases of serous vascularized (n = 7) and avascular (n = 3) PED, the FAF signal was increased, corresponding to the area of detachment. In drusenoid PED, the FAF was either increased or decreased. The decreased signal was recorded in cases associated with pigmented clumping. These findings are useful for a more detailed phenotyping of patients with PED associated with AMD. FAF may derive not only from lipofuscin, but also from other sources, such as sub-retinal pigment epithelium fluid.

Occult Chorioretinal Anastomosis in Age-Related Macular Degeneration: A Prospective Study by Optical Coherence Tomography

To investigate macular optical coherence tomography (OCT) features in patients with chorioretinal anastomosis (CRA) and drusen, as well as their correlation with the Gass occult-CRA hypothesis. Prospective observational case series. setting: Tertiary ophthalmic referral center. study population: All patients with biomicroscopic evidence of CRA and drusen consecutively evaluated between February 2003 and March 2004. observation procedures: Third-generation OCT evaluation and stereoscopic angiographic studies. main outcome measures: Macular morphologic features at baseline and at 12 weeks. Twenty eyes with CRA and drusen were identified in 11 patients, seven women (63.6%) and four men (36.4%) ranging in age from 69 to 82 years (median, 79 years). Focal elevation of the retinal pigment epithelium was seen in eyes with stage 1 (pre-clinical) CRA. Small hyperreflective signals at the level of the elevated retinal pigment epithelium were seen in stage 2 CRA. In stage 3 CRA, a hyperreflective "mound" at the level of the elevated retinal pigment epithelium was seen in association with a thickened retina. In stage 4 CRA sub-retinal pigment epithelium fluid accumulation was present, and complete disorganization of the macular region was observed in stage 5 CRA. Macular changes were observed in eight eyes (40%) at follow-up, with all but one CRA lesion progressing one stage. Morphologic features and changes demonstrated by OCT suggest that fibrovascular detachment of the retinal pigment epithelium followed by development of occult CRA are the initial events occurring in eyes with CRA in age-related macular degeneration. Our findings may support the evolutionary CRA staging system proposed by Gass.