Michael A. Klufas

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization

PURPOSE To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). CONCLUSIONS En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV.

OCT Angiography of Paracentral Acute Middle Maculopathy Associated With Central Retinal Artery Occlusion and Deep Capillary Ischemia.

An 82-year-old man presented with acute, painless vision loss in the left eye associated with headaches, jaw claudication, and scalp tenderness. Clinical examination and fluorescein angiography confirmed the diagnosis of a central retinal artery occlusion of the left eye. Spectral-domain optical coherence tomography (OCT) of the left eye showed paracentral acute middle maculopathy (PAMM), and OCT angiography showed severe attenuation of the deep capillary plexus. This is the first case report of OCT angiography of PAMM associated with central retinal artery occlusion confirming the presence of ischemia of the deep retinal capillary plexus.

Clinical applications of fundus autofluorescence in retinal disease

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

CORRELATION OF MULTIMODAL IMAGING IN SICKLE CELL RETINOPATHY

Purpose: To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. Methods: In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. Results: Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was S&bgr; thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and S&bgr; thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). Conclusion: Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.PURPOSE To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. METHODS In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. RESULTS Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was Sβ thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and Sβ thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). CONCLUSION Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.

Intravitreal anti-VEGF therapy as a treatment for retinopathy of prematurity: what we know after 7 years.

The authors review published clinical case reports, case series, and clinical trials evaluating the use of anti-vascular endothelial growth factor (VEGF) medications for the primary or adjunctive treatment of retinopathy of prematurity (ROP). A literature search of peer reviewed reports on PubMed was performed. More than 50 pertinent peer-reviewed publications between 2006 and 2014 were selected to be included in this review and are summarized in this report. There is a growing body of literature on the use of anti-VEGF therapy as a treatment for ROP, predominately in the form of case reports and small case series. Adverse effects from anti-VEGF treatment for ROP have been reported, but with limited follow-up time. The use of anti-VEGF as a treatment for ROP remains off-label.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF SICKLE CELL MACULOPATHY.

PURPOSE To report a case of sickle cell retinopathy imaged with optical coherence tomography angiography. METHODS Case report. RESULTS An asymptomatic 33-year-old man with known sickle cell anemia (SS) presented for routine eye examination. Ultrawide-field fluorescein angiography confirmed areas of temporal nonperfusion without neovascularization and subtle enlargement of the foveal avascular zone in the left eye. Spectral domain optical coherence tomography showed thinning of the inner layers of the temporal macula in both eyes. Optovue split-spectrum amplitude decorrelation angiography optical coherence tomography was performed and showed reduced flow within the superficial and deep macular plexuses of each eye, most severely within the deep retinal capillary plexus. This abnormality was more extensive than could it be appreciated with conventional angiography. CONCLUSION This report provides evidence that optical coherence tomography angiography may be more sensitive in detecting macular capillary nonperfusion than fluorescein angiography. It also provides further evidence that the ischemic vasculopathy of sickle cell retinopathy preferentially affects the deep capillary plexus.

Feasibility And Clinical Utility Of Ultra-widefield Indocyanine Green Angiography

Purpose: To evaluate the feasibility and clinical utility of a novel noncontact scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiographic system. Methods: Ultra-widefield indocyanine green angiographic images were captured using a modified Optos P200Tx that produced high-resolution images of the choroidal vasculature with up to a 200° field. Ultra-widefield indocyanine green angiography was performed on patients with a variety of retinal conditions to assess utility of this imaging technique for diagnostic purposes and disease treatment monitoring. Results: Ultra-widefield indocyanine green angiography was performed on 138 eyes of 69 patients. Mean age was 58 ± 16.9 years (range, 24–85 years). The most common ocular pathologies imaged included central serous chorioretinopathy (24 eyes), uveitis (various subtypes, 16 eyes), age-related macular degeneration (12 eyes), and polypoidal choroidal vasculopathy (4 eyes). In all eyes evaluated with ultra-widefield indocyanine green angiography, high-resolution images of choroidal and retinal circulation were obtained with sufficient detail out to 200° of the fundus. Conclusion: In this series of 138 eyes, scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiography was clinically practical and provided detailed images of both the central and peripheral choroidal circulation. Future studies are needed to refine the clinical value of this imaging modality and the significance of peripheral choroidal vascular changes in the diagnosis, monitoring, and treatment of ocular diseases.

Influence of Fluorescein Angiography on the Diagnosis and Management of Retinopathy of Prematurity

PURPOSE To examine the influence of fluorescein angiography (FA) on the diagnosis and management of retinopathy of prematurity (ROP). DESIGN Prospective cohort study. PARTICIPANTS Nine recognized ROP experts (3 pediatric ophthalmologists and 6 retina specialists) interpreted 32 sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images from infants with ROP. METHODS All experts independently reviewed the 32 image sets on a secure website and provided a diagnosis and management plan for the case presented, first based on color fundus photographs alone, and then based on color fundus photographs and corresponding FA images. MAIN OUTCOME MEASURES Sensitivity and specificity of the ROP diagnosis (zone, stage, plus disease, and category, i.e., no ROP, mild ROP, type 2 ROP, and ROP requiring treatment) were calculated using a consensus reference standard diagnosis, determined from the diagnosis of the color fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. The κ statistic was used to analyze the average intergrader agreement among experts for the diagnosis of zone, stage, plus disease, and category. RESULTS Addition of FA to color fundus photography resulted in a significant improvement in sensitivity for diagnosis of stage 3 or worse disease (39.8% vs. 74.1%; P = 0.008), type 2 or worse ROP (69.4% vs. 86.8%; P = 0.013), and pre-plus or worse disease (50.5 vs. 62.6%; P = 0.031). There was a nonsignificant trend toward improved sensitivity for diagnosis of ROP requiring treatment (22.2% vs. 40.3%; P = 0.063). Using the κ statistic, addition of FA to color fundus photography significantly improved intergrader agreement for diagnosis of ROP requiring treatment. Addition of FA to color fundus photography did not affect intergrader agreement significantly for the diagnosis of stage, zone, or plus disease. CONCLUSIONS Compared with color fundus photography alone, FA may improve the sensitivity of diagnosis of ROP by experts, particularly for stage 3 disease. In addition, intergrader agreement for diagnosis of ROP requiring treatment may improve with FA interpretation.

Variable Results for Uveal Melanoma–Specific Gene Expression Profile Prognostic Test in Choroidal Metastasis

IMPORTANCE We report our experience with uveal melanoma-specific gene expression profile (GEP) testing on a series of choroidal metastatic tumors confirmed by cytopathology so that clinicians may be aware that receiving a class 1 or class 2 test result in nonmelanoma is possible. OBSERVATIONS Retrospective review of all cytopathology and DecisionDx-UM GEP reports between January 2012 to December 2014 from intraoperative fine-needle aspiration biopsy of choroidal tumors undergoing brachytherapy. Four patients were identified to have cytopathology consistent with a nonmelanoma primary. All 4 patients presented with a unilateral, single choroidal tumor, which was treated with iodine-125 brachytherapy and underwent intraoperative fine-needle aspiration biopsy for cytopathology and uveal melanoma-specific GEP testing for molecular prognostication. Gene expression profile testing of the choroidal tumor in each patient revealed class 1A in 3 patients and class 2 in 1 patient. CONCLUSIONS AND RELEVANCE DecisionDx-UM GEP may be a helpful test for molecular prognostication in patients with uveal melanoma; however, class 1 and class 2 test results are indeed possible in the setting of a nonmelanoma malignancy. We recommend that cytopathology and/or other melanoma-specific testing be performed in all cases of suspected choroidal melanoma because GEP with this assay is unable to rule out the diagnosis of a choroidal melanoma.

Color Fundus Photography Versus Fluorescein Angiography in Identification of the Macular Center and Zone in Retinopathy of Prematurity

PURPOSE To examine the usefulness of fluorescein angiography (FA) in identifying the macular center and diagnosis of zone in patients with retinopathy of prematurity (ROP). DESIGN Validity and reliability analysis of diagnostic tools. METHODS Thirty-two sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images obtained from 16 eyes of 8 infants with ROP were compiled on a secure web site. Nine ROP experts (3 pediatric ophthalmologists and 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. MAIN OUTCOME MEASURES (1) Sensitivity and specificity of zone diagnosis and (2) computer-facilitated diagnosis of zone, based on precise measurement of the macular center, optic disc center, and peripheral ROP. RESULTS Computer-facilitated diagnosis of zone agreed with the experts diagnosis of zone in 28 (62%) of 45 cases using color fundus photographs and in 31 (69%) of 45 cases using FA images. Mean (95% confidence interval) sensitivity for detection of zone I by experts compared with a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA images was 47% (range, 35.3% to 59.3%) and 61.1% (range, 48.9% to 72.4%), respectively (t(9) ≥ (2.063); P = .073). CONCLUSIONS There is a marginally significant difference in zone diagnosis when using color fundus photographs compared with using color fundus photographs and the corresponding FA images. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic examination and image review) compared with a computer-facilitated diagnosis of zone.