Faculty Bibliography

IMPORTANCE Evidence is mounting that achromatopsia is a progressive retinal degeneration, and treatments for this condition are on the horizon. OBJECTIVES To categorize achromatopsia into clinically identifiable stages using spectral-domain optical coherence tomography and to describe fundus autofluorescence imaging in this condition. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was performed between 2010 and 2012 at the Edward S. Harkness Eye Institute, New York-Presbyterian Hospital. Participants included 17 patients (aged 10-62 years) with full-field electroretinography-confirmed achromatopsia. MAIN OUTCOMES AND MEASURES Spectral-domain optical coherence tomography features and staging system, fundus autofluorescence and near-infrared reflectance features and their correlation to optical coherence tomography, and genetic mutations served as the outcomes and measures. RESULTS Achromatopsia was categorized into 5 stages on spectral-domain optical coherence tomography: stage 1 (2 patients [12%]), intact outer retina; stage 2 (2 patients [12%]), inner segment ellipsoid line disruption; stage 3 (5 patients [29%]), presence of an optically empty space; stage 4 (5 patients [29%]), optically empty space with partial retinal pigment epithelium disruption; and stage 5 (3 patients [18%]), complete retinal pigment epithelium disruption and/or loss of the outer nuclear layer. Stage 1 patients showed isolated hyperreflectivity of the external limiting membrane in the fovea, and the external limiting membrane was hyperreflective above each optically empty space. On near infrared reflectance imaging, the fovea was normal, hyporeflective, or showed both hyporeflective and hyperreflective features. All patients demonstrated autofluorescence abnormalities in the fovea and/or parafovea: 9 participants (53%) had reduced or absent autofluorescence surrounded by increased autofluorescence, 4 individuals (24%) showed only reduced or absent autofluorescence, 3 patients (18%) displayed only increased autofluorescence, and 1 individual (6%) exhibited decreased macular pigment contrast. Inner segment ellipsoid line loss generally correlated with the area of reduced autofluorescence, but hyperautofluorescence extended into this region in 2 patients (12%). Bilateral coloboma-like atrophic macular lesions were observed in 1 patient (6%). Five novel mutations were identified (4 in the CNGA3 gene and 1 in the CNGB3 gene). CONCLUSIONS AND RELEVANCE Achromatopsia often demonstrates hyperautofluorescence suggestive of progressive retinal degeneration. The proposed staging system facilitates classification of the disease into different phases of progression and may have therapeutic implications.

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

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

PURPOSES:: To evaluate the multimodal imaging findings in retinal deep capillary ischemia (DCI). METHODS:: This was a retrospective review of 5 eyes of 4 patients with sudden onset of paracentral scotomas caused by DCI. Multimodal imaging techniques, including color and red-free photographs, near-infrared reflectance, fluorescein angiography, and spectral-domain optical coherence tomography, were performed in all eyes, and the findings were correlated with microperimetry in two eyes. Imaging findings in DCI were compared with those of a cotton wool spot caused by superficial capillary ischemia (SCI). RESULTS:: Unlike SCI, the imaging findings in DCI were subtler during both the acute and chronic phase, but specific optical coherence tomographic findings could readily differentiate these entities. Acute SCI showed inner retinal whitening, edema, and increased reflectivity, whereas acute DCI showed increased reflectivity of middle retinal layers. Chronic DCI showed retinal thinning with middle layer atrophy, whereas chronic SCI showed inner layer atrophy. In one patient, microperimetry showed a paracentral dense scotoma that corresponded well to the optical coherence tomographic findings. CONCLUSION:: Deep capillary ischemia may represent a nonspecific finding of retinal ischemia and produces characteristic changes within the middle retinal layers, analogous to a deep cotton wool spot, but with distinct features differing from the superficial cotton wool spot which is seen in SCI. Among the various multimodal imaging techniques, optical coherence tomography seemed to be the most sensitive and specific technique in detecting DCI in both the acute and chronic phases.

PURPOSE: To describe the nature and evolution of acquired macular detachments in patients with immunogammopathies and to propose a mechanism for their development. DESIGN: Retrospective observational case series. METHODS: Three patients with multiple myeloma and 1 with light chain deposition disease were diagnosed with vitelliform macular detachments based on clinical examination, fundus autofluorescence, fluorescein angiography, and optical coherence tomography. These patients were followed over time and their clinical examinations and imaging studies were compared and contrasted. RESULTS: Three patients (5 eyes) with multiple myeloma and 1 patient (2 eyes) with light chain deposition disease presented with acquired macular yellowish subretinal deposits on funduscopic examination that corresponded to hyperautofluorescent lesions on fundus autofluorescence imaging and subretinal hyperreflective material on spectral-domain optical coherence tomography. One patient (2 eyes) had diffuse serous retinal detachments involving not only the macular region but also the midperiphery of the retina. These acquired macular vitelliform detachments were not associated with signs of hyperviscosity retinopathy in 5 eyes and resolved after successful treatment of the multiple myeloma in 6 eyes. CONCLUSION: Patients with an immunogammopathy such as multiple myeloma or light chain deposition disease may develop serous elevations of the macula that we classify as acquired vitelliform detachments using multimodal imaging. Appropriate evaluation including serum protein electrophoresis and hematology consultation should be considered in the management of patients with acquired vitelliform detachments of uncertain etiology.

PURPOSE: To study clinical findings associated with acquired vitelliform lesions in retinal pigment epithelial detachments (PEDs). DESIGN: Retrospective, interventional, consecutive case series. METHODS: We retrospectively reviewed 32 eyes of 24 patients (22 men, 2 women; age range [mean], 58-85 [73.7] years) with acquired vitelliform lesions. RESULTS: All eyes had acquired vitelliform lesions in the central macula associated with a serous PED at baseline. Of the 32 eyes, 30 (93.8%) were observed for 12 months, 26 (81.3%) for 24 months, and 17 (53.1%) for 36 months. The mean logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA) levels were 0.19 at month 12, 0.28 at month 24, and 0.25 at month 36, none of which differed significantly from baseline. The mean changes in the BCVA were declines of 0.38, 1.29, and 1.21 lines at months 12, 24, and 36, respectively. Of 7 eyes treated with 3 consecutive monthly intravitreal injections of ranibizumab, the serous PEDs remained in all 7 eyes and the mean changes of BCVA were a decline of 2.40 lines 12 months after the first injection and a decline of 3.58 lines at the final visit. In the 24 untreated eyes, the mean change in the BCVA was a decline of 0.25 line at the final visit, which differed significantly (P = .021) compared with that of the treated eyes at the final visit. CONCLUSION: Intravitreal injections of ranibizumab were ineffective because of the absence of resolution of the PEDs and the declines in VA.

PURPOSE:: To describe the clinical characteristics and progression of patients with multifocal choroiditis lesions who had minimal or no evidence of anterior uveitis and/or vitritis. METHODS:: Retrospective, observational, single-center consecutive case series. Clinical histories, examination, and multimodal imaging findings were analyzed. RESULTS:: Sixty-five eyes of 41 patients were identified. The mean age at diagnosis was 38.4 years (median, 35 years; range, 15-81 years), and 70.7% of the patients were women. Involvement was bilateral in 21 patients (51.2%) at presentation. The 60-month bilateral event-free survival was 75.0% (95% confidence interval, 49.8-91.2%). The mean visual acuity was 20/46 (median, 20/25; range, 20/20 to count fingers at 2 feet) at presentation and 20/42 (median, 20/25; range, 20/20-5/400) at the last recorded visit. The 60-month "20/50 or worse" event-free survival was 100%. Between the first presentation and final follow-up (a mean duration of 92.6 months; range, 0-343 months), 46.7% of the eyes developed new or larger chorioretinal spots and 32.6% developed new or recurrent choroidal neovascularization. The 60-month choroidal neovascularization event-free survival was 68.1% (95% confidence interval, 39.2-85.4%). CONCLUSION:: Patients with multifocal choroiditis lesions, but with minimal or no anterior uveitis or vitritis, tended to be young women. Approximately half of the patients presented with bilateral involvement, which is less than has been reported in most case series of multifocal choroiditis with panuveitis. One quarter of all unilaterally affected patients will develop bilateral involvement by 60 months.

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.