Lisa J. Faia

Fundus Autofluorescence Imaging of the White Dot Syndromes

OBJECTIVE To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). METHODS Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. RESULTS Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P < .001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P < .001). CONCLUSIONS Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs.

High-dose Daclizumab for the Treatment of Juvenile Idiopathic Arthritis–Associated Active Anterior Uveitis

PURPOSE To provide preliminary data regarding the safety and efficacy of high-dose intravenous daclizumab (Zenapax; Roche Inc, Nutley, New Jersey, USA) therapy for the treatment of juvenile idiopathic arthritis (JIA)-associated active anterior uveitis. DESIGN Interventional case series; open-label prospective, phase II pilot study. METHODS Six patients were recruited into the study and received daclizumab therapy at doses of 8 mg/kg at baseline, 4 mg/kg at week 2, and 2 mg/kg every 4 weeks thereafter, for a total of 52 weeks. The study was done at the National Eye Institute between June 29, 2005 and July 9, 2008. The primary outcome was a two-step decrease in inflammation grade assessed at week 12. Primary safety outcome was assessed at weeks 2 and 4. The ocular inflammation was assessed according to the Standardization of Uveitis Nomenclature criteria. RESULTS Four of the 6 participants achieved two-step reduction in anterior chamber cells according to Standardization of Uveitis Nomenclature Working Group grading scheme for anterior chamber cells 12 weeks into the study and met the primary efficacy endpoint. One additional patient responded to reinduction whereas 1 patient failed reinduction and was considered an ocular treatment failure. Visual acuity improved from a mean of 68 Early Treatment Diabetic Retinopathy Study letters in the worse eye to a mean of 79.6 letters (2 Snellen lines). Three participants were terminated before 52 weeks: First, because of a rash possibly induced by daclizumab; Second, because of ocular treatment failure; and Last, because of uncontrolled systemic manifestations of JIA. CONCLUSION High-dose intravenous daclizumab can help reduce active inflammation in active JIA-associated anterior uveitis; however, patients need to be monitored for potential side effects. Larger randomized trials are needed to better assess treatment effect and safety.

A RANDOMIZED PILOT STUDY OF SYSTEMIC IMMUNOSUPPRESSION IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH CHOROIDAL NEOVASCULARIZATION

Background: Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. Methods: This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results: The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion: These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated.

Primary Intraocular Lymphoma

Primary intraocular lymphoma, recently suggested to be renamed primary retinal lymphoma, is a subset of primary central nervous system lymphoma and is usually an aggressive diffuse large B-cell lymphoma. Between 56% and 85% of patients who initially present with primary intraocular lymphoma alone will develop cerebral lesions. Patients typically complain of decreased vision and floaters, most likely secondary to the chronic vitritis and subretinal lesions. The diagnosis of primary intraocular lymphoma can be difficult to make and requires tissue for diagnosis. The atypical lymphoid cells are large and display a high nuclear to cytoplasmic ratio, prominent nucleoli, and basophilic cytoplasm. Flow cytometry, immunohistochemistry, cytokine analysis, and gene rearrangements also aid in the diagnosis. Local and systemic treatments, such as chemotherapy and radiation, are employed, although the relapse rate remains high.

Long-term daclizumab therapy for the treatment of noninfectious ocular inflammatory disease

OBJECTIVE Safety and efficacy of daclizumab during an 11-year period. DESIGN Structured, retrospective chart review. PARTICIPANTS Thirty-nine patients. METHODS Patients with chronic, noninfectious intermediate and/or posterior uveitis. RESULTS Thirty-nine patients (78 eyes) were treated for a mean of 40.3 months. Visual acuity improved by ≥2 lines in the better eye in 7 patients (18.4%) and worsened by 2 lines in 6 patients (15.8%) with a mean of 2.8 Snellen lines of vision lost per eye. Six eyes with vitreous cell less than grade 2 lost 2 lines of vision and 7 eyes with less than grade 2 vitreous cell improved 2 lines. Mean number of immunosuppressive medications per patient decreased from 1.89 medications/patient to 1.17 medications/patient. The average number of periocular injections per patient was 1.46 (range, 0-9). The mean number of flares was 2.05/patient (range, 0-12), with the rate being 0.62 flares per patient-year. Four patients developed cancer during the course of this study. Mean time to onset of malignancy was 26 months and the mean age in this group was 49 years. CONCLUSIONS Daclizumab demonstrated efficacy in the reduction of concomitant immunosuppressive medication, stabilization of visual acuity, and the prevention of uveitic flares in most cases. Dermatologic complications were the most frequently observed adverse event in our series. Four patients developed solid tumor malignancies during this 11-year period.

Advances in the diagnosis and immunotherapy for ocular inflammatory disease.

Significant advances in the diagnosis and therapy for uveitis have been made to improve the quality of care for patients with ocular inflammatory diseases. While traditional ophthalmic examination techniques, fluorescein angiography, and optical coherence tomography continue to play a major role in the evaluation of patients with uveitis, the advent of spectral domain optical coherence tomography and fundus autofluorescence into clinical practice provides additional information about disease processes. Polymerase chain reaction and cytokine diagnostics have also continued to play a greater role in the evaluation of patients with inflammatory diseases. The biologic agents, a group of medications that targets cytokines and other soluble mediators of inflammation, have demonstrated promise in targeted immunotherapy for specific uveitic entities. Their ophthalmic indications have continued to expand, improving the therapeutic armentarium of uveitis specialists.

Uveitic Foveal Atrophy: Clinical Features and Associations

OBJECTIVE To characterize foveal atrophy in a heterogeneous group of patients with uveitis using clinical findings and high-definition (HD) optical coherence tomography (OCT). DESIGN Cross-sectional, retrospective case series. RESULTS The HD-OCT scans of 140 patients seen in a tertiary referral center were reviewed and 23 patients (33 eyes) with foveal atrophy were identified. All of the patients with foveal atrophy were diagnosed with intermediate uveitis, posterior uveitis, or panuveitis. The status of the photoreceptor layer as visualized with HD-OCT was associated with significant differences in mean visual acuity (P < .001). Clinical findings associated with foveal atrophy included atrophy of the retinal pigment epithelium and choroid (30 eyes [91%]), macular ischemia (13 eyes [39%]), cystoid macular edema (5 eyes [15%]), choroidal neovascularization (4 eyes [12%]), retinal detachment involving the macula (2 eyes [6%]), and serum antiretinal antibodies (2 eyes [6%]). CONCLUSIONS Foveal atrophy can be a complication of intraocular inflammation in a variety of uveitic syndromes. The cause of foveal atrophy is multifactorial and may include dysfunction and atrophy of the retinal pigment epithelium and choroid, cystoid macular edema, macular ischemia secondary to occlusive retinal vasculitis, choroidal neovascularization, retinal detachment, and possibly antibody-mediated damage directed against photoreceptors. Careful observation of the photoreceptor layer using HD-OCT may help to identify patients who are at risk for visual loss secondary to foveal atrophy.

A Case of Autoimmune Retinopathy Associated with Thyroid Carcinoma

Purpose: To report a case of autoimmune retinopathy (AIR) associated with a thyroid carcinoma. Design: Case report. Method: A 51-year-old Caucasian woman presented with a rapid decline in vision. Initial visual field and immunohistochemical testing revealed autoimmune retinopathy without an apparent underlying malignancy. Conventional local and systemic immunosuppressive therapies failed to halt the progression. Results: Rituximab treatments were initiated and a slowing of visual loss was seen. Continued surveillance for malignancy revealed a thyroid adenoma, and later a thyroidectomy revealed a thyroid carcinoma. Conclusions: This report highlights the unique presentation of AIR associated with a thyroid carcinoma, the need for continued surveillance for malignancy in cases of AIR, and the possible new use of rituximab for the treatment of AIR.

Lack of Consensus in the Diagnosis and Treatment for Ocular Tuberculosis among Uveitis Specialists

Abstract Purpose: To assess the approach of specialists to ocular tuberculosis (TB). Methods: The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Results: Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1–75%) or that a patient with a risk factor for TB had ocular TB (range 0–90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Conclusions: Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Fundus Autofluorescence Patterns in Primary Intraocular Lymphoma

Purpose: To evaluate fundus autofluorescence (FAF) patterns in patients with primary intraocular (vitreoretinal) lymphoma. Methods: Records of all patients with primary intraocular lymphoma who underwent FAF imaging at the National Eye Institute were reviewed. Fundus autofluorescence patterns were evaluated with respect to clinical disease status and the findings on fluorescein angiography and spectral-domain optical coherence tomography. Results: There were 18 eyes (10 patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal autofluorescence in the form of granular hyperautofluorescence and hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary intraocular lymphoma at the time of imaging, but there were 5 eyes with unremarkable FAF, which were found to have active lymphoma. The most common pattern on fluorescein angiography was hypofluorescent round spots with a “leopard spot” appearance (43%). These hypofluorescent spots on fluorescein angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%) (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment epithelium on optical coherence tomography were noted in 43% of eyes. The hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots on optical coherence tomography in 6 eyes (43%). Conclusion: Granularity on FAF was associated with active lymphoma in majority of the cases. An inversion of FAF (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on fluorescein angiography) was observed in less than half of the eyes.