Monica Dalal

Comparison of Wide-Field Fluorescein Angiography and 9-Field Montage Angiography in Uveitis

PURPOSE To compare qualitatively and quantitatively Optos fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in patients with uveitis. DESIGN Retrospective, observational case series. METHODS Images of all patients with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9-month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage. RESULTS The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P < 0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25% less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were 2 eyes that had no apparent retinal vascular leakage in 9-field montage but were found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the Optos image. A single 200-degree Optos FA image captured a mean 1.50× the area captured by montage photography. CONCLUSIONS More retinal vascular pathology, in both the periphery and the posterior pole, is seen with Optos FA in patients with uveitis when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.

Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

PURPOSE To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN Modified Delphi process. METHODS A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. RESULTS There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Neoplastic masquerade syndromes in patients with uveitis.

PURPOSE To identify the demographic and clinical characteristics, along with the frequency, of neoplastic masquerade syndromes in a tertiary uveitis clinic. DESIGN A retrospective observational cohort. METHODS Demographic and clinical data on all patients presenting to the National Eye Institute (NEI) with uveitis between 2004 and 2012 were used to compare neoplastic masquerade syndromes and uveitis. RESULTS A total of 853 patients presenting with uveitis were identified. Of these, 21 (2.5%) were diagnosed with neoplastic masquerade syndromes. The average age at presentation of masquerade syndrome patients was 57 years (median, 55; range, 38-78); for uveitis, 42 years (median, 43; range, 3-98) (P = 0.0003). There were 48% females in the masquerade syndromes group, compared with 59% females in the uveitis group. African American patients represented 9% of the masquerade syndrome patients and 36% of uveitis patients (P = 0.01). Mean worse eye visual acuity was 0.89 (20/160) in neoplastic masquerade syndromes, and 0.66 (20/100) in the uveitis group (P = 0.21). Of masquerade syndrome patients, 90% had posterior inflammation, compared with 63% of uveitis patients (P = 0.006). Of those with masquerade syndromes, 48% of patients had unilateral disease, compared with 27% of the uveitis patients (P = 0.04). CONCLUSIONS Patients with neoplastic masquerade syndromes were more likely to be older, male, or non-African American and to have posterior segment inflammation and unilateral disease. Patients with masquerade syndromes also had worse visual acuity than did uveitis patients. These differences in clinical characteristics may help to raise the suspicion for neoplastic masquerade syndromes.

Diagnosis of Occult Melanoma Using Transient Receptor Potential Melastatin 1 (TRPM1) Autoantibody Testing: A Novel Approach

PURPOSE To report the first case of melanoma-associated retinopathy (MAR) and underlying occult melanoma diagnosed based on the presence of serum transient receptor potential melastatin 1 (TRPM1) autoantibodies. DESIGN Interventional case report with basic science correlation. PARTICIPANTS One patient with MAR. INTERVENTION Testing for the presence of serum TRPM1 autoantibodies. MAIN OUTCOME MEASURES Diagnosis of an occult melanoma involving the axillary lymph nodes (unknown primary site) and MAR based on the presence of TRPM1 autoantibodies in the patients serum. RESULTS The patients clinical exam was remarkable for mild intraocular inflammation in both eyes and retinal hemorrhages with an apparent choroidal neovascularization in the left eye, which was confirmed by fluorescein angiography and indocyanine green angiography testing. Humphrey visual field 30-2 SITA-fast (Humphrey Visual Field Analyzer, Carl Zeiss Meditec, Inc, Dublin, CA) demonstrated diffuse depression in both eyes out of proportion to the clinical exams, prompting electroretinography testing that revealed an electronegative response. Dark-adapted thresholds were markedly elevated and mediated by cones. Due to concern for MAR, a systemic work-up for melanoma was performed by the primary care physician that was unrevealing. Given our continued clinical suspicion for MAR, the patients serum was sent for evaluation for TRPM1 autoantibodies. The patients serum applied to normal human retina exhibited positivity in the inner nuclear layer. Application of the patients serum to wild-type and TRPM1 knockout mouse retina revealed strongly labeled bipolar cells in the wild-type retina, but not in the TRPM1 knockout retina, indicating TRPM1-dependent immunoreactivity. The antigen was confirmed as TRPM1 by labeling of TRPM1-transfected human embryonic kidney 293 cells. Additional systemic work-up prompted by this finding resulted in identification of an occult metastatic melanoma involving the axillary lymph nodes with an unknown primary site. The patient underwent surgical excision of the occult melanoma without evidence of other sites of metastases. He also received intravenous immunoglobulin therapy and his vision has stabilized. CONCLUSIONS This is the first reported case of a melanoma-associated retinopathy diagnosed utilizing the innovative approach of testing for serum TRPM1 autoantibodies.

Subconjunctival Sirolimus in the Treatment of Autoimmune Non-necrotizing Anterior Scleritis: Results of a Phase I/II Clinical Trial

PURPOSE To investigate the safety, tolerability and efficacy of subconjunctival sirolimus injections as a treatment for active, autoimmune, non-necrotizing anterior scleritis. DESIGN Phase I/II, single-center, open-label, nonrandomized, prospective pilot study. METHODS Five participants with active, autoimmune, non-necrotizing anterior scleritis with scleral inflammatory grade of ≥1+ in at least 1 quadrant with a history of flares were enrolled. A baseline injection was given, with the primary outcome measure of at least a 2-step reduction or reduction to grade zero in the study eye by 8 weeks. Secondary outcomes included changes in visual acuity and intraocular pressure, ability to taper concomitant immunosuppressive regimen, and number of participants who experienced a disease flare requiring reinjection. Safety outcomes included the number and severity of systemic and ocular toxicities, and vision loss ≥15 ETDRS letters. The study included 6 visits over 4 months with an extension phase to 1 year for participants who met the primary outcome. RESULTS All participants (N = 5, 100%; 95% CI [0.60, 1.00]) met the primary outcome in the study eye by the week 8 visit. There was no significant change in mean visual acuity or intraocular pressure. Three out of 5 patients (60%) experienced flares requiring reinjection. No systemic toxicities were observed. Two participants (40%) experienced a localized sterile inflammatory reaction at the site of the injection, which resolved without complication. CONCLUSIONS Subconjunctival sirolimus leads to a short-term reduction in scleral inflammation, though relapses requiring reinjection do occur. There were no serious adverse events, though a local sterile conjunctival inflammatory reaction was observed.

Diagnostic Procedures in Vitreoretinal Lymphoma

Abstract Purpose: To evaluate the type and number of diagnostic interventions needed to confirm the presence of vitreoretinal lymphoma. Method: Chart review of interventions performed for diagnosis of vitreoretinal lymphoma. Results: Of the 27 cases, diagnosis was made by pars plana vitrectomy in 13 (48.1%), vitreous tap in 2 (7.4%), anterior chamber tap in 1 (3.7%), chorioretinal biopsy in 2 (7.4%), brain biopsy in 5 (18.5%), and cerebrospinal fluid cytology via lumbar puncture in 4 (14.8%). Ten (37%) had definitive results on the first procedure, and 17 (63%) had at least one false negative. Vitrectomy was the most common procedure performed. Patients required a mean of 2.1 procedures. Average time from onset of symptoms to confirmed histopathologic diagnosis was 13.9 months. Conclusion: Vitreoretinal lymphoma is difficult to recognize and requires a high degree of clinical suspicion. It often takes more than one invasive procedure to make the diagnosis.

Ophthalmic Issues in Chronic Kidney Disease

Ophthalmic pathology and kidney diseases are intricately linked. Patients with CKD encounter well-known ophthalmic diseases such as retinopathy at a rate that exceeds the general population, particularly those with diabetic kidney disease. Furthermore, ophthalmic disease in patients with CKD tends to manifest with greater severity compared to those with normal kidney function. Beyond diabetes, there are a host of inherited and acquired diseases with both kidney and ophthalmic phenotypes. Often, a thorough ophthalmic evaluation can solidify or unify a diagnosis in a timely fashion and may even prevent unnecessary invasive procedures. Given the complexity and severity of these diseases, it appears prudent to involve the care of ophthalmology in the care of many more CKD patients, extending beyond the relationship ophthalmologists already have with diabetic patients. Future studies are clearly needed to better define the relationship and treatment of ophthalmic complications in the setting of CKD.

Chapter 55 – Ocular Disease

Uveitis consists of inflammation of the iris, ciliary body, and choroid. Anatomical location, type of inflammation, and demographic features are important factors for elucidating the underlying etiology. The presence of uveitogenic antigens in the human eye have been established, and are thought to incite disease in conjunction with disarray of the immune system. Several elements including genetics, hormones, and environmental influences are thought to play a role in the development of uveitis. Experimental autoimmune uveitis (EAU) has been important for studying the molecular mechanisms involved, including the role of cellular immunity and cytokines. While many treatment options for uveitis exist, the continued understanding of the disease process allows for more tailored therapies.