Faculty Bibliography

PURPOSE: To describe the spectrum of retinal capillary ischemia, including superficial and deep capillary ischemia, as identified with spectral-domain optical coherence tomography (SD-OCT) that occurs in retinal arterial occlusive disease. DESIGN: Retrospective observational case series METHODS: Clinical charts, color fundus photography, red-free fundus photography, fluorescein angiography, near-infrared reflectance and SD-OCT imaging in 40 eyes of 35 patients with retinal arterial occlusive disease were studied in both the acute and chronic phases in multicenter clinical practices. SD-OCT imaging analysis was employed to characterize the presence of superficial and deep capillary ischemia in each eye. RESULTS: Of the 40 eyes, 15 eyes had central retinal artery occlusion (CRAO), 22 eyes had branch retinal artery occlusion (BRAO) and 3 eyes had cilioretinal artery occlusion. During the acute phase, SD-OCT showed the following 3 distinct patterns, related to retinal ischemia occurring at varying levels within the retina: 1. Thickening and hyper-reflectivity of the inner retinal layers, including the nerve fiber and ganglion cell layers due to ischemia of the superficial capillary plexus; 2. A hyper-reflective band at the level of the inner nuclear layer, termed "paracentral acute middle maculopathy" representing ischemia of the intermediate and deep retinal capillary plexuses (deep capillary ischemia); and 3. Diffuse thickening and hyper-reflectivity of both the inner and middle retinal layers, which represented both superficial and deep capillary ischemia. Of all eyes, 31 (78%) had both superficial and deep lesions. The remaining 9 (22%) eyes had isolated deep capillary ischemia producing paracentral acute middle maculopathy with sparing of the superficial capillary plexus and a normal fluorescein angiographic appearance. As the lesions evolved into the chronic phase over the ensuing 3 months, the resultant thinning and atrophy reflected the retinal layers affected during the acute phase. CONCLUSION: SD-OCT imaging reveals the spectrum of capillary ischemia in retinal artery occlusive disease showing variable involvement of the superficial and intermediate/deep capillary plexuses. Isolated deep capillary ischemia manifested as paracentral acute middle maculopathy on SD-OCT and may be seen in some eyes with retinal arterial circulation compromise despite complete absence of perfusion abnormalities on fluorescein angiography.

Purpose: To assess the etiologies and clinical outcomes associated with pattern dystrophy (PD) with multimodal imaging. Methods: Consecutive cases with the diagnosis of PD followed by a physician (LAY) underwent a comprehensive ophthalmologic examination including visual acuity (VA), color fundus and fundus autofluorescence photographs, infrared reflectance imaging, and spectral domain and enhanced depth optical coherence tomography. Correlations were made between the etiologies of PD and the age at diagnosis, VA at diagnosis and last follow-up, choroidal thickness (CT), subfoveal central macular thickness (CMT), and the number with outer retinal disruption (ORD) of the ellipsoid layer. Results: 81 patients (113 eyes) (42% male) with a mean (+/-SD) age 72.9 years (+/-12.6, range 39-92) were diagnosed with PD and had a mean follow-up duration of 40.5 months (+/-47.7, range 0-280). The etiologies of PD were age-related macular degeneration (AMD), central serous chorioretinopathy (CSCR), epiretinal membrane (ERM) with vitreomacular traction (VMT), and acquired vitelliform macular dystrophy (VMD) with each having an incidence of 55(48.7%), 5(4.4%), 12(10.6%), and 41(36.3%), respectively. The mean VA at diagnosis was 20/77.5, 20/27, 20/65.8, and 20/41.1, and at last follow-up was 20/77.5, 20/29, 20/170, and 20/67.3 for AMD, CSCR, ERM, and VMD, respectively. There was not a significant difference in BCVA at diagnosis and follow-up among the different etiologies of PD (p=0.27, 0.69, 0.28, 0.10, respectively). Mean CT(+/-SD) was 201.6(+/-77.5), 255.4(+/-119.7), 131.3(+/-73.4), and 240.9(+/-86.3) for AMD, CSCR, ERM, and VMD, respectively. Mean CMT(+/-SD) was 311.1(+/-58.5), 288.6(+/-70.7), 328.3(+/-50.5), and 286.4(+/-52.6) for AMD, CSCR, ERM, and VMD, respectively. The number with ORD was 30(54.5%), 2(40.0%), 5(41.7%), and 20(48.7%) for AMD, CSCR, ERM, and VMD respectively. ERM/VMT had an overall thinner choroid (p<0.005) but there was no difference in overall mean CMT (p=0.06) or number with ORD (p=0.80). Conclusions: Patients with PD are most likely to have AMD or VMD. Mean initial and final VA remained stable in AMD, CSCR, ERM/VMT, and VMD although ERM/VMT showed a statistically insignificant decrease in final VA. The CMT or the number with ORD was not significantly different among the diagnoses although ERM/VMT did demonstrate a significantly thinner choroid, which along with the VMT, may partially explain the overall decrease in vision

Purpose To assess the cone photoreceptor mosaic in acute macular neuroretinopathy(AMN) using adaptive optics(AO) imaging. Methods Four consecutive patients with AMN were evaluated by dilated funduscopic examination, near-infrared reffectance(IR), confocal scanning laser ophthalmoscopy(SLO), eye-tracked spectral-domain optical coherence tomography(SDOCT) and a flood-illuminated retinal AO camera. Correlations were made between IRSLO, SDOCT and AO images at baseline and follow-up in 3 patients. Microperimetry was performed and correlated with SDOCT and AO images in 1 patient. Results At presentation, the cone photoreceptor density was decreased at the level of the AMN lesions in AO images in all patients. The cone photoreceptor mosaic disruption was more widespread than the lesion detected by IRSLO and SDOCT. At complete resolution of the AMN lesion in IRSLO, there was incomplete recovery of cone photoreceptor mosaic in AO. In 2 cases, there was persistent cone damage in AO despite restoration of the ellipsoid zone integrity on SDOCT at last follow-up. The area of disruption in cone mosaic revealed characteristic appearance of RPE cells in AO and correlated well with both SDOCT and microperimetry findings. Conclusions Cone photoreceptor damage and reconstitution were documented in vivo at the cellular level in AMN using AO imaging. AO appeared more sensitive than combined IRSLO and SDOCT to detect and follow photoreceptor damage in AMN patients. There was some irreversible cone photoreceptor damage in the 4 patients evaluated

The authors describe fundus autofluorescence (AF) and spectral-domain optical coherence tomography (SD-OCT) findings in three patients with enhanced S-cone syndrome and their correlation around the hyperautofluorescent ring border. Patients had AF imaging in combination with SD-OCT line-scans through the fovea, at the posterior pole, and at a temporal locus centered on the ring border. All eyes demonstrated a macular ring of high-intensity AF. The inner segment ellipsoid band showed thinning and disorganization toward the ring border, where it was lost. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:592-595.].

BACKGROUND AND OBJECTIVE: To assess the cone photoreceptor mosaic in acute macular neuroretinopathy (AMN) using adaptive optics (AO) imaging. PATIENTS AND METHODS: Four patients with AMN were evaluated retrospectively by near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO), spectral-domain optical coherence tomography (SD-OCT), and a flood-illuminated retinal AO camera. Microperimetry was performed in one patient. RESULTS: The cone photoreceptor density was decreased at the level of the AMN lesions. The cone mosaic disruption appeared heterogeneous and more widespread than the lesion detected in the IR-SLO and SD-OCT images. The areas of cone loss correlated with SD-OCT and microperimetry. After resolution of the AMN lesion on IR-SLO, there was incomplete recovery of the cone photoreceptor mosaic. CONCLUSION: Cone photoreceptor damage and reconstitution were documented in vivo at the cellular level in AMN using AO imaging. AO imaging appeared more sensitive than combined IR-SLO and SD-OCT to detect and follow photoreceptor damage in patients with AMN. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:562-569.].

PURPOSE: To represent and evaluate the findings of bilateral perifoveal macular ischemia in a patient with biopsy-proven, multiorgan involved sarcoidosis. METHODS: Case report. A 55-year-old man, with a medical history of pulmonary disease, experienced reduced vision bilaterally. General ocular examination, fundus color photographs, fluorescence angiography, and high-resolution spectral domain optical coherence tomography were performed in both eyes. RESULTS: The patient's visual acuity was 20/200 in the right eye and 20/30 in the left eye with normal intraocular pressure and anterior segment. Fundus examination showed symmetric changes with the loss of transparency in macular and small intraretinal hemorrhages in both eyes. Fluorescence angiography demonstrated markedly enlarged avascular zone while optical coherence tomography revealed marked cystic change in the macula bilaterally. A series of blood test was conducted without a specific diagnosis. A lung biopsy confirmed the diagnosis of pulmonary sarcoidosis, and a magnetic resonance imaging of his brain revealed neurosarcoidosis. CONCLUSION: Bilateral perifoveal ischemia, formerly one of the three idiopathic macular telangiectasia diseases, is rare and usually suggests a systemic etiology. It is not unexpected that sarcoidosis, a multisystem, chronic inflammatory disorder, may affect retinal vessels and be associated with this peculiar form of ischemia and edema.

PURPOSE: To report a case of idiopathic multifocal choroiditis with transient peripapillary zonal inflammation that was followed with multimodal imaging and explain the mechanism by which chorioretinal atrophy may occur. METHODS: Observational case report. Review of the clinical examination, ocular imaging, and progression of idiopathic multifocal choroiditis. RESULTS: A 30-year-old white myopic man presented with complaints of worsening vision and a loss of visual field for 1 month in his left eye. Using multimodal imaging, including wide-field imaging with fluorescein angiography, fundus autofluorescence, and high-definition spectral-domain optical coherence tomography, he was found to have a macula involving peripapillary zonal inflammation consistent with acute idiopathic multifocal choroiditis involving the outer photoreceptor layer, ellipsoid layer, retinal pigment epithelium, and choroid. This area of inflammation was monitored with multimodal imaging over 7 months and slowly improved along with the patient's vision. Imaging allowed us to view the development of chorioretinal scars from several, but not all, acute inflammatory white spots. CONCLUSION: Multifocal choroiditis is an inflammatory disorder affecting the outer photoreceptors, ellipsoid layer, retinal pigment epithelium, and choroid; and areas of acute inflammation may improve over time but can also leave permanent chorioretinal atrophy including focal lesions or peripapillary zonal atrophy.

PURPOSE: To describe the nature and evolution of paraneoplastic cloudy vitelliform submaculopathy in patients with primary vitreoretinal lymphoma and propose a mechanism for its development and course. DESIGN: Retrospective, observational case series. METHODS: Three patients presenting with unilateral cloudy vitelliform submaculopathy based on clinical examination, fundus autofluorescence, fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT) imaging and ultimately diagnosed with primary vitreoretinal lymphoma and/or primary central nervous system lymphoma were analyzed. RESULTS: In all 3 patients, cloudy vitelliform submaculopathy appeared with hazy indistinct yellow subretinal material resembling the vitelliform lesions found in acute exudative paraneoplastic polymorphous vitelliform maculopathy, however with less distinct appearance and without intense hyperautofluorescence. In all 3 patients, cloudy vitelliform submaculopathy was transient, showed spontaneous regression within 3 months and preceded the diagnosis of lymphoma, suggestive of a paraneoplastic process. The diagnosis of primary vitreoretinal lymphoma and/or primary central nervous system lymphoma was made within 6 months with classic features of new intraretinal or sub-retinal pigment epithelium infiltration of lymphoma in the peripheral retina (n=2) and hyperintense lesions on brain magnetic resonance imaging (n=2). With SD-OCT imaging, the cloudy vitelliform subretinal lesions appeared as hyper-reflective debris above the retinal pigment epithelium band in all 3 eyes, and were associated with an irregularly thickened and rippled retinal pigment epithelium band in 2 eyes. Resolution of the cloudy submacular lesions resulted in outer retinal atrophic changes in all 3 eyes. CONCLUSION: Paraneoplastic cloudy vitelliform submaculopathy, a form of lymphoma associated retinopathy, can precede the diagnosis of primary vitreoretinal lymphoma or primary central nervous system lymphoma and can regress spontaneously, leaving outer retinal abnormalities.

Autosomal recessive Stargardt disease (STGD1) is caused by hundreds of mutations in the ABCA4 gene, which are often specific to racial and ethnic groups. Here, we investigated the ABCA4 variation and their phenotypic expression in a cohort of 44 patients of African American descent, a previously under-characterized racial group. Patients were screened for mutations in ABCA4 by next-generation sequencing (NGS) and array-comparative genome hybridization (aCGH), followed by analyses for pathogenicity by in silico programs. Thorough ophthalmic examination was performed on all patients. At least two (expected) disease-causing alleles in the ABCA4 gene were identified in 27 (61.4%) patients, one allele in 11 (25%) patients, and no ABCA4 mutations were found in 6 (13.6%) patients. Altogether, 39 different disease-causing ABCA4 variants, including 7 new, were identified on 65 (74%) chromosomes, most of which were unique for this racial group. The most frequent ABCA4 mutation in this cohort was c.6320G>A (p.(R2107H)), representing 19.3% of all disease-associated alleles. No large copy number variants were identified in any patient. Most patients reported later onset of symptoms. In summary, the ABCA4 mutation spectrum in patients of West African descent differs significantly from that in patients of European descent, resulting in a later onset and 'milder' disease