Lawrence A. Yannuzzi

Analysis of vascularized pigment epithelial detachments using indocyanine green videoangiography.

Background: Occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is known to occur with and without an associated serous pigment epithelial detachment (PED). Digital indocyanine green (ICG) videoangiography has been reported to provide enhanced definition of occult CNV. Methods: A total of 244 of 657 (37%) consecutive patients with AMD, with occult CNV and an associated serous PED evident on fluorescein angiographic examination, were further studied with ICG videoangiography. Results: On ICG videoangiographic examination, 9 of the 244 (4%) eyes had no evidence of underlying CNV, or essentially a pure serous PED. Each of the remaining 235 eyes (96%) had evidence of neovascularization and were defined as having a vascularized PED. These eyes were further divided into two groups, depending on the size and delineation of the neovascularization seen. Of the 235 eyes with vascularized PEDs, 89 (38%) had a solitary area of neovascularization that was well delineated, no more than one disc area in size, and defined as focal CNV. The other 146 (62%) eyes had a larger area of neovascularization, with variable delineation, defined as plaque CNV. Based on conventional guidelines, some patients were considered to be potentially eligible for laser photocoagulation treatment. Conclusion: The results of this study suggest that ICG videoangiography may be an important adjunct to the diagnosis, classification, and potential treatment of patients with AMD and occult CNV associated with a serous PED (vascularized PED).

Treatment of subfoveal choroidal neovascularization associated with multifocal choroiditis and panuveitis with photodynamic therapy.

Purpose To study the effects of photodynamic therapy (PDT) using verteporfin on the treatment of patients with subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis and panuveitis (MCP), an uncommon disorder with no proven forms of therapy. Methods A retrospective chart review of seven consecutive patients with subfoveal CNV secondary to MCP treated with PDT using verteporfin was performed. Results The mean age of the 7 patients (all myopic women) was 41.4 years. A mean of 1.86 treatments was performed, and the mean follow-up time was 10 months. Four of the seven patients were treated unsuccessfully with corticosteroids before referral for PDT. The mean improvement of visual acuity was 0.86 line; 3 patients (42.8%) had an improvement in visual acuity representing at least a halving of their visual angle, while the other 4 patients remained stable. There were no treatment-related side effects. Conclusions Although the follow-up time and the number of patients in this study were limited, the use of PDT was associated with stabilization or improvement of visual acuity in patients with subfoveal CNV secondary to MCP. Further study of this treatment modality is indicated.

Association Between Geographic Atrophy Progression and Reticular Pseudodrusen in Eyes With Dry Age-Related Macular Degeneration

PURPOSE To evaluate geographic atrophy (GA) progression in eyes with dry AMD and to determine factors related to GA expansion, notably reticular pseudodrusen (RPD), also known as subretinal drusenoid deposits (SDD) or reticular macular disease (RMD). METHODS This was a retrospective cohort study of patients with dry AMD who were diagnosed with GA in at least one eye and were imaged with sequential fundus autofluorescence (FAF) and/or near infrared reflectance (NIR-R) imaging. Images were analyzed for the presence of GA within the macular region. Geographic atrophy progression was measured in the fields of a modified Wisconsin grid and spatially correlated with RPD. Factors also evaluated for association with GA progression included initial GA size and pattern. RESULTS The study sample included 126 eyes of 92 patients, with an average follow up of 20.4 months (SD = 11.7). At baseline, 93.6% of eyes had RPD, and the average GA area was 2.8 mm(2) (SD = 2.9). The average GA progression rate was 0.8 mm(2)/y (SD = 0.6), with a statistically significant difference between the unilobular and multilobular phenotype groups (0.3 mm(2)/y vs. 0.9 mm(2)/y, P = 0.02). Patients in the lower 50th percentile of initial GA area had a lower progression rate than patients in the upper 50th percentile (0.6 mm(2)/y vs. 1.1 mm(2)/y, P < 0.001). Geographic atrophy progression was more frequent in fields with RPD than in those without RPD (74.2% vs. 41.7%, P < 0.001). CONCLUSIONS The high correlation between the presence of RPD (also known as SDD or RMD) and the presence of GA, and the expansion of GA into areas with these lesions suggest that they are an early manifestation of the process leading to GA.

Multiple evanescent white dot syndrome in patients with multifocal choroiditis.

Background Controversy exists as to whether a common causal entity is responsible for multifocal choroiditis (MFC) and multiple evanescent white dot syndrome (MEWDS). It is commonly known that patients with MEWDS can later develop manifestations of MFC, but the reverse is rarely seen. Purpose To report cases of MEWDS in patients previously diagnosed with MFC. Design Retrospective case series. Participants Four female patients 29 to 34 years old. Methods The charts of four patients with acute unilateral onset of MEWDS and evidence of previous MFC were examined retrospectively. Main Outcome Measures Photographic and angiographic interpretation of fundus appearance. Results At the time of diagnosis with typical MEWDS, one patient had a documented previous episode of acute MFC; one patient had previous bilateral choroidal neovascularization associated with discrete, posterior atrophic scars; and two patients had peripheral discrete chorioretinal pigmented lesions and peripapillary atrophy. Conclusions MEWDS may occur after MFC. Now that both directions of disease progression, MFC to MEWDS and MEWDS to MFC, have been well documented, it is likely that there is a common host susceptibility between these two distinct clinical diseases, if not a common pathogenesis.

Acute Zonal Occult Outer Retinopathy: A Classification Based on Multimodal Imaging

IMPORTANCE We describe the multimodal imaging in a group of patients showing a distinct clinical entity that best represents acute zonal occult outer retinopathy (AZOOR). OBJECTIVE To propose a classification of AZOOR based on clinical fundus and multimodal imaging. DESIGN, SETTING AND PARTICIPANTS A retrospective review of patients diagnosed as having AZOOR at 2 centers. After reviewing more than 400 cases diagnosed or referred to us as AZOOR or AZOOR complex, we assembled 30 cases that fit our current definition; (48 eyes) with a median age at diagnosis of 47 years (age range, 17-86 years) and a mean follow-up period of 39 months. Twenty patients were female. Eighteen patients had initially been seen with bilateral lesions, mostly asymmetric (4 cases were symmetric). Most patients had no remarkable medical or ocular history. The median visual acuity at the time of presentation was 20/25 (range, 20/20 to 20/400). MAIN OUTCOMES AND MEASURES Multimodal imaging, including fundus photography, fluorescein and indocyanine green angiography, fundus autofluorescence imaging, and corresponding eye-tracked spectral-domain coherence tomography imaging. RESULTS Each patient was initially seen with visual symptoms of photopsia and scotoma, and most had a detectable lesion in the fundus evident clinically or detected on multimodal imaging. The clinical appearance of the AZOOR lesions varied depending on their duration and location, but some features were characteristic, including a demarcating line of the progression at the level of the outer retina and a trizonal pattern of sequential involvement of the outer retina, retinal pigment epithelium, and choroid, as well as frequent zonal progression. Advanced cases of AZOOR demonstrated disruption of the inner and outer retina and severe damage or loss of the retinal pigment epithelium and the choroid. CONCLUSIONS AND RELEVANCE A specific definition of AZOOR based on multimodal imaging is proposed to help physicians distinguish it from other diseases of the posterior fundus, including white spot syndromes and autoimmune, hereditary, paraneoplastic, toxic, and other inflammatory retinopathies.

Anecortave acetate treatment for retinal angiomatous proliferation: a pilot study.

Purpose: The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. Methods: Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. Results: The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. Conclusion: The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy.

Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy

Purpose We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). Methods A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. Results The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 × 10-3) and deep (P = 2.653 × 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 × 10-5) and deep (P = 3.120 × 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. Conclusions The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.

Endoscopic vitreoretinal surgery for complicated proliferative diabetic retinopathy.

Purpose To evaluate the indication for endoscopic vitreoretinal surgery in proliferative diabetic retinopathy (PDR). Methods Chart review of consecutive cases of vitreoretinal surgery for PDR performed by one of the authors (Y.L.F.) over a 2-year period. Results Endoscopic vitreoretinal surgery was performed in 8 of 41 (19.5%) eyes. The surgical indications were small pupil (3), hyphema (3), pseudophakia with fibrotic posterior capsule (1), and pars plana neovascularization with anterior tractional retinal detachment (6). Conclusion Endoscopic vitreoretinal surgery, by enhancing the visualization of the retroirideal space, is a useful technique in PDR with opaque ocular media and/or neovascularization of the pars plana and ciliary body.

Expanded clinical spectrum of multiple evanescent white dot syndrome with multimodal imaging

Purpose: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. Methods: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. Results: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14–49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. Conclusion: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Retinal angiopathy and polypoidal choroidal vasculopathy.

Purpose To describe the clinical and angiographic features of patients with polypoidal choroidal vasculopathy, exudative detachment of the macula, and an associated retinal microangiopathy. Methods Case series. Results Four patients with chronic exudative detachment of the macula with a variable degree of lipid deposition are described. The retina in the detached area, but not beyond, was noted to have a microangiopathy. There was capillary telangiectasia, microaneurysm formation, patchy nonperfusion, and intraretinal leakage. In each patient, there were no other retinal vascular changes in the fundus of either eye. The fluorescein angiogram showed subretinal leakage suspicious for occult choroidal neovascularization. The indocyanine green angiogram showed the presence of underlying polypoidal choroidal neovascularization, accounting for the exudative detachment. After photocoagulation, the retinal angiopathy improved, but not completely. Conclusion Retinal microangiopathy may occur in a chronic macular detachment secondary to polypoidal choroidal neovascularization. The development of these secondary retinal changes is not clearly understood; however, hypoxia from the chronic detachment, a neurotoxic effect from the lipid deposition, or a biochemically induced microvascular abnormality from secretion of vasogenic mediators are possible mechanisms. Indocyanine green angiography is helpful in making a definitive diagnosis. Clinicians should be aware that a retinal microangiopathy may occur in such eyes so that the proper diagnosis can be made and appropriate treatment administered.