Setting Of Age-related Macular Degeneration Research Articles

No association between cataract surgery and mitochondrial DNA damage with age-related macular degeneration in human donor eyes.

To determine whether age-related macular degeneration (AMD) severity or the frequency of retinal pigment epithelium mitochondrial DNA lesions differ in human donor eyes that have undergone cataract surgery compared to phakic eyes. Eyes from human donors aged ≥ 55 years were obtained from the Minnesota Lions Eye Bank. Cataract surgery status was obtained from history provided to Eye Bank personnel by family members at the time of tissue procurement. Donor eyes were graded for AMD severity using the Minnesota Grading System. Quantitative PCR was performed on DNA isolated from macular punches of retinal pigment epithelium to quantitate the frequency of mitochondrial DNA lesions in the donor tissue. Univariable and multivariable analyses were performed to evaluate for associations between (1) cataract surgery and AMD severity and (2) cataract surgery and mitochondrial DNA lesion frequency. A total of 157 subjects qualified for study inclusion. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that only age was associated with AMD grade. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that none of these factors were associated with retinal pigment epithelium mitochondrial DNA lesion frequency. In this study of human donor eyes, neither retinal pigment epithelium mitochondrial DNA damage nor the stage of AMD severity are independently associated with cataract surgery after adjusting for other AMD risk factors. These new pathologic and molecular findings provide evidence against a relationship between cataract surgery and AMD progression and support the idea that cataract surgery is safe in the setting of AMD.

Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration

The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.

Quantitation of Total and Free Thiol β2-Glycoprotein I Levels for Diagnostic and Prognostic Purposes in the Antiphospholipid Syndrome.

β2-Glycoprotein I is the major autoantigen in the antiphospholipid syndrome (APS), a prothrombotic disorder characterized by the occurrence of either venous or arterial thrombosis. In women it is also associated with an increased risk of obstetric complications such as recurrent miscarriages. We have identified that the plasma protein β2-glycoprotein I in healthy individuals exists in an optimal ratio between two distinct forms, an oxidized and free thiol, reduced form. This ratio is disrupted in pathophysiological conditions associated with increased oxidative stress such as the APS, but also in the setting of age-related macular degeneration and gram-negative sepsis. We have developed assays that quantify plasma/serum levels of total and free thiol β2-glycoprotein I which can potentially be used for risk stratification and prognostic purposes in the early stages of the aforementioned conditions.

Nascent Type 3 Neovascularization in Age-Related Macular Degeneration

To describe the preclinical and very early stages of type 3 neovascularization using multimodal retinal imaging to expand our understanding of the pathogenesis of this disorder and potentially to prevent late treatment. Retrospective cohort study. Patients diagnosed with treatment-naïve type 3 neovascularization in the setting of age-related macular degeneration were identified at 4 retina referral centers. Inclusion criteria were: patients older than 55 years with at least 1 OCT and OCT angiography (OCTA) examination before the onset of clinically active type 3 neovascularization (i.e., preclinical stage). Patients underwent a complete ophthalmologic examination including at least OCT and OCTA at the baseline and preclinical stage examinations, and dye angiographies when available. Demographics and clinical findings were analyzed. Description of multimodal imaging features of nascent type 3 neovascularization. Fifteen eyes (15 patients; mean age, 83 ± 9 years) were included. At the baseline, mean BCVA was 0.32 ± 0.17 logarithm of the minimum angle of resolution and central macular thickness was 313 ± 50 μm. Preclinical (i.e., prebaseline) structural OCT illustrated the presence of intraretinal hyperreflective foci (HRF) at the site of type 3 neovascularization development in all patients. These foci were characterized by hyperfluorescence on dye angiography and by detectable flow on OCTA, identified with either the avascular slab (20%) or with both the deep retinal capillary plexus (DCP) and avascular slabs (80%). Typically, HRF with detectable flow on OCTA were characterized by the absence of intraretinal exudation (or very mild microcystic changes) until the lesion progressed from the DCP into the retinal pigment epithelium (RPE) and sub-RPE space. Of note, in 1 patient we observed the complete resolution of HRF despite the presence of OCTA flow and dye angiography hyperfluorescence detected at the preclinical stage examination. Hyperreflective foci on structural OCT may represent early intraretinal neovascularization originating from the DCP, namely nascent type 3 neovascularization; these lesions can progress to active type 3 neovascularization or more rarely may regress without functional impairment. An advanced multimodal imaging approach is useful in detecting nascent type 3 lesions, which should be followed up carefully and treated as soon as possible if flow progresses to the RPE and sub-RPE space to prevent progression to late stages.

Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3

To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Consensus meeting. Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. A consensus classification system for atrophy and OCT-based criteria to identify atrophy. OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.

Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD)

PurposeTo evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA).DesignProspective non-interventional study.MethodsConsecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two...

Correlation of Type 1 Neovascularization Associated With Acquired Vitelliform Lesion in the Setting of Age-Related Macular Degeneration

To correlate postmortem histology with previously recorded multimodal imaging from a patient with type 1 neovascularization (NV) associated with an acquired vitelliform lesion in the setting of age-related macular degeneration (AMD). Case study. Multimodal imaging that was obtained antemortem was matched with exvivo and high-resolution histologic images of the preserved donor macula. Anatomic correlates for multimodal imaging findings were then defined. Spectral-domain optical coherence tomography (OCT) revealed a split in the retinal pigment epithelium-Bruch membrane band. Type 1 NV in this case was composed of 6 layered components: (1) retinal pigment epithelium, (2) basal laminar deposits, (3) fibrovascular membrane, (4) fibrocellular scar, (5) hemorrhage, and (6) Bruch membrane. The anatomic correlates for the hyporeflective band on spectral-domain OCT included a thick basal laminar deposit. Not all structures could be readily separated on the basis of their reflectivity patterns. This is an important clinicopathologic correlation of NV secondary to AMD in the spectral-domain OCT era. Our findings of 6 layers include and extend the anatomic framework encapsulated by the double-layer and triple-layer signs. The resolution of current devices does not always permit distinction of the different layers of NV tissue. Thick basal laminar deposits may appear hyporeflective on spectral-domain OCT and may be confused with fluid from a neovascular process. It will be important to perform a larger clinicopathologic series to aid our anatomic interpretation of spectral-domain OCT images.

Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?

Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (β2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of β2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate β2GPI in the retina and choroid of patients with AMD. Free thiol β2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of β2GPI and free thiol bovine serum albumin were not protective. Free thiol β2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol β2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.

Intravitreal aflibercept use in the treatment of macular edema from central retinal vein occlusion

Aflibercept is a recently US FDA-approved anti-VEGF agent designed for intravitreal injection. Anti-VEGF agents have recently been demonstrated to be potent inhibitors of neovascular growth and vascular permeability in large clinical trials. The majority of studies of anti-VEGF agents are in the setting of age-related macular degeneration, but studies looking at diabetic macular edema and macular edema from central retinal vein occlusion (CRVO) and branch retinal vein occlusion are increasing the scope of utility of anti-VEGF drugs. Aflibercept for single-use intravitreal injection has been approved in the setting of age-related macular degeneration and in macular edema caused by CRVO in the USA (approval has been sought in Europe). The purpose of this review is to examine the use of aflibercept in the setting of CRVO and the role it may potentially play in the expanding indications for anti-VEGF agents.

Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

PURPOSE: To report the response of choroidal neovascularization (CNV) to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD) with extensive pre-existing geographic atrophy (GA) and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT) analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab) for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti-VEGF therapy for subfoveal CNV, presumably due to the limitation in the baseline visual acuity caused by the underlying GA. The good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results were consistent with other ranibizumab studies.

Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy

To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existing geographic atrophy. Patients were included if they had geographic atrophy at or adjacent to the foveal center of at least 1 disc area in size that was present before the development of choroidal neovascularization. The best corrected visual acuity and optical coherence tomography analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab or bevacizumab were administered until there was complete resolution of subretinal fluid on optical coherence tomography. Data over the entire follow-up period were analyzed for overall visual and optical coherence tomography changes. The patients received an average of 7 ± 3 intravitreal injections over the treatment period. Seven of 11 eyes had reduced retinal thickening on optical coherence tomography. On average, the central macular thickness was reduced by 72 ± 115 µm. Six of these 7 eyes had improvement of one or more lines of vision and one had no change. The average acuity change for all patients was -0.04 ± 0.46 logMAR units, which corresponded to a gain of 0.2 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with resolution of the subretinal fluid and overall stable visual acuity. The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab or bevacizumab) for choroidal neovascularization in age-related macular degeneration with pre-existing geographic atrophy is effective. Our results are not as striking as published results from large-scale trials of anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization, presumably due to the limitation in the baseline visual acuity caused by the underlying geographic atrophy. The favorable anatomic response with the resolution of subretinal fluid and stable acuity were consistent with other ranibizumab and bevacizumab studies.

Automated Characterization of Pigment Epithelial Detachment by Optical Coherence Tomography

To assess the accuracy of automated classification of pigment epithelial detachments (PED) by using a software algorithm applied to spectral-domain optical coherence tomography (SD-OCT) scans. HD-OCT (Cirrus; Carl Zeiss Meditec, Dublin, CA) volume scans (512 × 128) were retrospectively collected from 46 eyes of 33 patients with evidence of PED in the setting of age-related macular degeneration (AMD, n = 28) or central serous chorioretinopathy (CSCR, n = 5). In these eyes, 168 PEDs were automatically detected with a system-associated tool (Cirrus HD-OCT RPE Elevation Analysis; Carl Zeiss Meditec). Two independent, certified Doheny Image Reading Center (DIRC) OCT graders classified these PEDs into three categories--serous, drusenoid, or fibrovascular--via inspection of the B-scans. Manual classification results served as the gold standard for comparisons with automated classification. For automated classification, interindividual variation in intensities was normalized in all images. Individual A-scans within the detected PEDs were then automatically classified into one of three categories based on the mean internal intensity and the standard deviation of the internal intensity: mean intensity <30 (serous type); mean intensity ≥30 but <60 or mean intensity ≥30 and SD ≥30 (fibrovascular type); or mean intensity ≥60 and SD < 30 (drusenoid type). Individual PEDs were then automatically classified into the same three categories based on the predominant type of A-scan within the PED. For mixed PEDs (many A-scans of each type), a risk index for neovascularization was computed based on the percentage of fibrovascular A-scans. In addition, a confidence index was computed for each PED based on its mathematical distance from the PED category boundaries. Among the 168 PEDs, the DIRC graders classified 16 as serous, 88 as fibrovascular, and 64 as drusenoid PEDs. The automated algorithm classified 14 as serous, 96 as fibrovascular, and 58 as drusenoid PEDs. The sensitivity and specificity values for automated classification according to type of PED were 88% and 100% for serous, 76% and 64% for fibrovascular, and 58% and 81% for drusenoid, respectively. Automated classification of PEDs using internal reflectivity characteristics appears to be sensitive for detecting serous and fibrovascular PEDs. Automated classification and quantification of PEDs may be a useful tool in future studies for stratifying PEDs according to risk and possibly predicting the risk of advanced AMD.

Fluorescein and ICG angiograms : still a gold standard

Abstract Purpose: To review the role of Fluorescein Angiography and ICG in the management of ARMD Methods: Fundus Fluorescein Angiography (FFA) is the gold standard for classification of Choroidal Neovascular Membranes (CNVMs) in Age Related Macular Degeneration (ARMD). CNVMs may be defined as classic, minimally classic or occult by their filling patterns observed on angiography. The findings of the large TAP and VIP studies are based on angiographically defined CNVMs. FFA in the setting of ARMD is indicated when the patient complains of new metamorphopsia, experiences unexplained blurred vision or there is evidence of subretinal fluid, haemorrhages or hard exudates1,2 .Fluorescein Angiography is an invasive procedure and carries a risk of anaphylaxis and death. There should be on site facilities readily available to manage any potential complications of an FFA.Indocyanine Green Angiography (ICG) is used to evaluate the choroidal circulation and is of particular use in the diagnosis of Idiopathic Polypoidal Choroidal Vasculopathy. Results: With the advent of new therapeutic modalities there is a need for frequent monitoring of the response of the CNVM to treatment. Ocular Coherence Topography complements FFAs and ICG, reducing the number of angiograms required during the quiescent phase of treatment. In spite of this invasive angiography remains the gold standard for diagnosis and treatment Conclusions: References1 Summary benchmarks for Preferred Practice Benchmarks in the Setting of ARMD. www.aao.org2 International Clinical Guidelines for ARMD. www.icoph.org

Angiographic and flow patterns of retinal choroidal anastomoses in age-related macular degeneration with occult choroidal neovascularization

Objective To identify the angiographic features of retinal choroidal anastomoses (RCAs) in patients with newly diagnosed occult choroidal neovascularization (CNV) in the setting of age-related macular degeneration (AMD) and to determine the sequence of flow between the RCA and the CNV. Design Retrospective cross-sectional study. Participants The angiograms of 205 eyes of 153 consecutive patients with occult CNV on fluorescein angiography (FA) and focal hot spots on indocyanine green angiography (ICGA) were evaluated retrospectively. Methods of testing Red-free photographs and sequential digital fluorescein and indocyanine green angiograms obtained by confocal scanning laser ophthalmoscope (the Heidelberg Retina Angiograph; Heidelberg Engineering GmbH, Dossenheim, Germany). Main outcome measures The angiograms were evaluated for the presence of RCA. The following angiographic characteristics were recorded: number and type of anastomoses, location, distance from fovea, area of CNV, presence of pigment epithelium detachment (PED), cystoid macular edema on FA, and intraretinal leakage on ICGA. The direction of flow between the RCA and the CNV was identified by analyzing high-speed angiograms. Results Retinal choroidal anastomoses were identified in 57 eyes (28%), in 49 of 154 eyes with PED (32%), and in 8 of 51 eyes without PED (16%). Of 109 anastomoses, 70% were venous and 30% were arterial. Ninety-six percent of the eyes had at least one venous anastomosis, 49% of the eyes had an arterial anastomosis, and 46% of the eyes had both. Cystoid macular edema was seen on FA in 37 eyes (65%), and intraretinal indocyanine green leakage was noted in 52 eyes (91%). Twenty-two eyes that underwent high-speed ICGA were analyzed for the direction of flow. All 15 eyes having arterial and venous anastomoses demonstrated a filling pattern from the retinal arteriole to the CNV, followed by the retinal venule. Seven eyes with venous RCA showed flow sequence from the CNV to the collecting retinal venule. Conclusions Our study supports the presence of RCA in the early stages of acute exudative AMD with occult CNV, mainly with serous PED. High-speed angiography helps to identify the filling sequence of the RCA and the CNV, and therefore may guide the clinician in planning treatment strategies.

Simultaneous indocyanine green and fluorescein angiography in retinal pigment epithelium tear using the confocal scanning laser ophthalmoscope

PURPOSE: To describe the indocyanine green angiographic pattern of retinal pigment epithelium tears in the setting of age-related macular degeneration compared with the fluorescein angiographic features. METHODS: Twelve consecutive patients (12 eyes) with a retinal pigment epithelium tear underwent simultaneous indocyanine green angiography and fluorescein angiography with the confocal scanning laser ophthalmoscope. The findings for the two modes were compared. RESULTS: Choroidal neovascular membrane was evident beneath the rolled retinal pigment epithelium on indocyanine green angiograms in 11(92%) of 12 eyes: a focal neovascular membrane was apparent in five (42%) of 12 eyes, whereas a plaque neovascular membrane was seen in six (50%) of 12 eyes. In comparison, fluorescein angiography demonstrated late leakage as a result of occult choroidal neovascular membrane in nine (82%) of 11 eyes but no well-defined choroidal neovascular membrane. CONCLUSIONS: Indocyanine green angiography is superior to fluorescein angiography for imaging choroidal neovascularization in cases of retinal pigment epithelium tear and may serve as an important adjunct to indocyanine green–guided laser treatment in selected cases.