Naomi Goldberg

Redefining multifocal choroiditis and panuveitis and punctate inner choroidopathy through multimodal imaging.

Purpose: To evaluate the characteristics of multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) using multimodal imaging. Methods: This is a retrospective, consecutive, observational case series of 38 eyes of 22 patients. Each eye of patients with multiple yellow-white idiopathic inflammatory lesions in the fundus was classified as having MCP or PIC using standard diagnostic criteria in a masked fashion. The features of these eyes as determined from color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and angiography were compared across diagnostic categories. The main outcome measures were the features of both MCP and PIC as evidenced by multimodal imaging. Results: Of the 38 eyes, 23 eyes had MCP, 15 had PIC; and 7 patients had a discordant pairing of one diagnosis in 1 eye with the other diagnosis in the fellow eye. Acute lesions appeared as nodular collections under the retinal pigment epithelium. These solid retinal pigment epithelium detachments appeared to rupture leading to inflammatory infiltration of the subretinal space and outer retina, often with a widespread loss of the outer retinal architecture beyond the confines of the inflammatory exudate. Treatment with corticosteroids caused a rapid regression of this material with a slower resolution of the abnormalities of the outer retinal architecture. The pattern of inflammatory involvement seen by multimodal imaging did not vary between PIC and MCP. No consistent abnormalities were seen in the choroid in either condition, although there was slight thickening of the choroid underlying some acute lesions. Conclusion: Despite the names of these diseases, the principle sites involved appears to be the subretinal pigment epithelium and outer retinal spaces. Because both MCP and PIC target the same essential structures in the same phenotypic manner and, when active, are treated the same way, there seems to be limited clinical utility in trying to differentiate them. Based on multimodal imaging results, a reappraisal of pathogenic features and naming conventions of these diseases seems indicated.

Outer Retinal Tubulation in Degenerative Retinal Disorders

Purpose: To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders. Methods: This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of ORT and its evolution over time were analyzed using spectral-domain optical coherence tomography data. Results: Outer retinal tubulation was identified as round or ovoid structures with hyperreflective borders in pattern dystrophy (six eyes), acute zonal occult outer retinopathy (five eyes), retinitis pigmentosa (four eyes), Stargardt disease (four eyes), gyrate atrophy (two eyes), choroideremia (two eyes), and various other degenerative conditions. These structures appeared to develop from the invagination of photoreceptors at the junction of intact and atrophic outer retina. During follow-up, the number and distribution of ORT largely remained stable. As zones of atrophy enlarged, the frequency of ORT appeared to increase. The ORT structures were found in <10% of patients with retinitis pigmentosa, Stargardt disease, or pattern dystrophy. Conclusion: Outer retinal tubulation is found in various degenerative retinal disorders that share in common damage to the outer retina and/or retinal pigment epithelium. The presence of ORT may be an indicator of underlying disease stage and severity.

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

Purpose: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. Methods: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. Results: Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. Conclusion: The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

Subretinal Fluid in Uveitic Macular Edema: Effect on Vision and Response to Therapy

PURPOSE To evaluate the effect of subretinal fluid (SRF), imaged with spectral-domain optical coherence tomography (SD-OCT), on visual acuity outcomes in cases of uveitic macular edema (ME), and to analyze the response of SRF and uveitic ME to therapy. DESIGN Retrospective case series. METHODS One hundred and one eyes of 75 patients with uveitic ME, as imaged by SD-OCT, were identified at a single tertiary-care referral center. The main outcome measures were best-corrected visual acuity, central subfield thickness (CSFT), and rates of macular edema improvement (≥20% reduction in CSFT), and resolution (defined as reduction of CSFT to <315 μm) of ME at 3 and 6 months follow-up. RESULTS Forty eyes of 29 patients had SRF on SD-OCT at presentation, which was associated with greater macular thickness (mean CSFT 488 μm vs 362 μm, P = .0001) and worse visual acuity than ME without SRF (20/115 vs 20/51, P = .015). However, eyes with SRF responded more favorably to treatment, and at 3 and 6 months of follow-up they achieved greater rates of improvement and resolution of ME than eyes without SRF (77% improved and 50% resolved at 6 months, vs 20% and 13%, respectively; P = .003 and P = .017, respectively) and recovered to a similar level of visual acuity (20/62 vs 20/42 at 6 months, P = .54). CONCLUSIONS SRF in uveitic ME is associated with thicker retinas and worse visual acuity on presentation but responds more favorably to treatment and displays greater rates of edema resolution and visual acuity improvement.

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.

New best1 mutations in autosomal recessive bestrophinopathy.

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.

Success with single-agent immunosuppression for multifocal choroidopathies.

PURPOSE To evaluate the success of single-agent immunosuppression for patients with the posterior uveitides, birdshot chorioretinitis, multifocal choroiditis with panuveitis, and punctate inner choroiditis. DESIGN Retrospective case series. METHODS setting: Tertiary care uveitis practices. population: Patients initiated on immunomodulatory therapy. intervention: Patients were treated with prednisone 1 mg/kg and mycophenolate 2 g daily. Prednisone was tapered after 1 month. Immunosuppression was escalated to mycophenolate 3 g daily, with addition of a second agent, as needed, to achieve treatment success. outcome measure: Treatment success, defined as no disease activity with prednisone dose ≤10 mg daily, at 6, 12, and 24 months. RESULTS Twenty-seven patients were followed. Mean presentation and 2-year follow-up acuities were 20/41 and 20/42, respectively. For birdshot chorioretinitis, mean (±standard deviation) quantitative Goldmann visual field scores improved from 761 ± 69 degrees (IV/4 isopter) and 496 ± 115 degrees (I/4 isopter) at presentation to 784 ± 57 degrees and 564 ± 125 degrees, respectively. Prednisone was successfully tapered in 95% of patients; mean prednisone doses at 1 and 2 years were 5.3 ± 4.1 and 5.7 ± 4.8 mg/day, respectively. At 2 years, prednisone was discontinued in 11% of patients. Treatment success was achieved in 74% of patients on 1 immunosuppressant, and in an additional 21% of patients on 2 agents, for an overall 95% success rate at 2 years. CONCLUSIONS Posterior uveitides can be treated with 1 agent in most patients, but the data suggest a need to escalate therapy to higher mycophenolate doses, and in one fifth of cases to add a second agent to maintain disease suppression with acceptably low prednisone doses.

Progression of an Acquired Vitelliform Lesion to a Full-Thickness Macular Hole Documented by Eye-Tracked Spectral-Domain Optical Coherence Tomography

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Optical Coherence Tomography Imaging of Presumed Sarcoid Retinal and Optic Nerve Nodules

Abstract Purpose: To characterize nodular lesions of the retina and optic nerve with spectral-domain optical coherence tomography (SD-OCT) in patients with sarcoidosis. Methods: This is a retrospective series of 6 eyes from 5 patients with an established diagnosis of sarcoidosis, with clinically detected nodules of the optic nerve or retina. All lesions were imaged with fundus photography and SD-OCT on presentation, and followed with serial imaging after treatment with corticosteroids and/or immunomodulatory therapy. Results: Spectral OCT through the lesions revealed nodular hyperreflective processes obscuring the retinal layers or optic cup, with local structural changes, including subretinal and intraretinal fluid. After treatment with corticosteroids and/or immunosuppression in 4 followed patients, all lesions regressed with improvement in associated structural changes, but did not entirely disappear. Conclusions: Spectral OCT can be useful in identifying lesion morphology and location, and in tracking the response to treatment in eyes with posterior-segment nodules, presumably secondary to sarcoidosis.