Faculty Bibliography

Purpose To determine the rate of neovascularization (NV) in eyes with acquired vitelliform lesion (AVL) during and following vitelliform collapse. To correlate the optical coherence tomography (OCT) and histopathological characteristics of these neovascular membranes. Methods Retrospective cohort analysis of 112 patients with AVL. Patients that demonstrated evidence of vitelliform collapse, defined as a temporal reduction in the size of subretinal vitelliform material clinically, using OCT and fundus autofluorescence imaging, were included for further analysis. Clinical and OCT characteristics of neovascular membranes were determined. A correlation between OCT and histopathological characteristics of an eye that was clinically diagnosed as non-neovascular but demonstrated a type 1 membrane on post mortem examination was also performed. Results Twenty-six patients (16 males and 10 females) demonstrated evidence of vitelliform collapse, and 7 (26.9%) of these developed NV. 5 of these patients were diagnosed with NV following acute subretinal hemorrhage or exudation. Mean age of patients was 81.1 +/- 11.6 years, and mean period of follow up was 9.0 +/- 4.2 years. All neovascular membranes were type 1. Persistent OCT findings prior to the development of NV included: (1) Irregular elevation of the retinal pigment epithelium (RPE) layer at the site of NV. (2) Separation of the RPE layer and Bruch's membrane (BrM) by a hyporeflective material containing punctate hyper-reflectivity (figure 1). Three patients had fluorescein angiography (FA) within 6 months preceding the diagnosis of neovascular disease that did not demonstrate leakage. Histopathologic examination demonstrated a fibrovascular scar and thick basal laminar deposit (BlamD) under the fovea with hemorrhage between the scar and BrM. These lesions correlated with the split RPE-BrM band on OCT images acquired 8 months before the patient's death (figure 2). Conclusions The rate of Type 1 NV during and following vitelliform collapse in AVLs is significant. In this subgroup of patients, neovascular membranes appear to remain dormant in the anatomic space between BrM and BLamD before the clinical signs of NV, including exudation and hemorrhage, become manifest. Interval review of these patients is therefore indicated as is a prospective study of this topic

PURPOSE:: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS:: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS:: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. CONCLUSION:: Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy-associated dominant mutations.

BACKGROUND:: To report the presence of transient peripapillary serous detachments in multiple evanescent white dot syndrome. METHODS:: Retrospective case series. RESULTS:: Four eyes of four patients diagnosed with multiple evanescent white dot syndrome presented with peripapillary serous detachments. Diagnosis was based on clinical presentation, fundus findings, and angiographic findings. All 4 were female with age ranges between 24 and 40 years and presented with photopsias, an enlarged scotoma contiguous with the blind spot, and chorioretinal white dots in the posterior pole with characteristic angiographic features. All of the serous detachments resolved or were greatly reduced concomitantly with the resolution of the patient's other clinical symptoms and fundus findings. CONCLUSION:: The authors report peripapillary serous detachments as a previously unreported manifestation of multiple evanescent white dot syndrome. These seem to be self limited with concurrent resolution with the rest of the patient's symptoms.

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.

BACKGROUND: We present a case of a combined hamartoma of the retina and retinal pigment epithelium associated with a subfoveal acquired vitelliform lesion induced by vitreomacular traction. The purpose of this report is to present a unifying hypothesis of these concurrent findings, as aided by multimodal imaging. CASE PRESENTATION: A 25-year-old white man presented with a 6-month history of a visual disturbance in his left eye. At presentation, ophthalmic assessment showed a combined hamartoma adjacent to his optic nerve that had caused marked corrugation within the inner retinal surface. An acquired vitelliform lesion was present in the macula with an associated epiretinal membrane as demonstrated on spectral-domain optical coherence tomography. Optical coherence tomography angiography corroborated the clinical diagnosis of combined hamartoma. CONCLUSIONS: We are not aware of previous cases of a combined hamartoma associated with an acquired vitelliform lesion. As previously proposed in acquired vitelliform lesions related to epiretinal membrane and vitreoretinal traction, we believe that macular tractional forces might interfere with retinal pigment epithelium phagocytosis of shed outer segments, leading to the occurrence of this acquired vitelliform lesion.

PURPOSE:: To describe multimodal imaging findings in a patient with foveal red spot syndrome. METHODS:: We report a case of a 57-year-old man with foveal red spot syndrome. Multimodal imaging techniques, including fundus color and red-free photographs, fluorescence angiography (Topcon 50DX; Topcon, Tokyo, Japan), MultiColor scanning laser imaging, spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany), swept source optical coherence tomography (DRI OCT-1 Atlantis; Topcon, Tokyo, Japan), adaptive optics (RTX-1; Imagine Eyes, Orsay, France), and microperimetry (MP1 Microperimeter; Nidek Technologies, Padua, Italy), were performed to confirm the diagnosis and determine the anatomical abnormalities related to the disease. RESULTS:: Conventional clinical examination and imaging studies failed to explain the patient's visual dysfunction and this specific macular abnormality. Using advanced ophthalmic technologies, including MultiColor imaging, spectral domain optical coherence tomography with high-density acquisition, swept source optical coherence tomography, adaptive optics, and microperimetry, we identified the nature of the macular manifestation accounting for pathology of the foveal red spot syndrome and his visual dysfunction. CONCLUSION:: When conventional clinical examination and imaging techniques fail to identify the presence of and visual symptoms in foveal red spot syndrome, advanced technologies may be used to confirm the diagnosis and explain the etiology of the abnormality.

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.