Andrea D. Birnbaum

Ocular disease in pregnancy.

Purpose of review Pregnancy may cause ocular changes, both physiologic and pathologic, and may be associated with the development of new disease or may alter the course of preexisting disease. This paper discusses these changes and reviews diabetic retinopathy, uveitis, preeclampsia, cortical blindness and central serous chorioretinopathy. Recent findings Recent reports have contributed to our understanding of the pathophysiology of diabetic retinopathy and cortical blindness associated with preeclampsia, the impact of pregnancy on the course of inflammatory eye disease, and the use of optical coherence tomography in following central serous chorioretinopathy in pregnant women. Summary This improved understanding of the pathophysiology of ocular disease in pregnancy and the impact of pregnancy on the course of preexisting ocular disease offers the opportunity for meaningful counseling of women who are pregnant or planning to become pregnant.

Clinical Features and Diagnostic Evaluation of Biopsy-Proven Ocular Sarcoidosis

OBJECTIVES To compare the clinical characteristics of uveitic sarcoidosis in African American and non-African American patients with biopsy-proven sarcoidosis and to determine which diagnostic test results were most often suggestive of sarcoidosis in patients who were ultimately diagnosed as having the disease. METHOD Retrospective review of consecutive patients with biopsy-proven sarcoidosis evaluated by the uveitis service between 1989 and 2009. RESULTS A total of 63 patients with uveitic sarcoidosis were identified: 39 (62%) were African American (P <.001) and 43 (68%) were female. African American patients presented at an earlier age (P <.001) and were more likely to have granulomatous anterior segment inflammation (P <.001). The levels of serum markers angiotensin-converting enzyme and lysozyme were elevated in 40% and 42% of patients tested, respectively. The levels of at least 1 marker were elevated in 18 patients (58%). Imaging study results were reported as consistent with sarcoidosis in 25 patients (69%) who underwent chest radiography and in 19 patients (100%) who underwent computed tomography. CONCLUSIONS In this series, African American patients were more likely to be diagnosed as having uveitic sarcoidosis and to present with uveitis if they were younger than 50 years. White patients were more likely to present when they were older than 50 years. A clinical picture that included granulomatous anterior segment inflammation was more common in African American patients. The use of serum markers (angiotensin-converting enzyme and lysozyme) positively identified more patients with biopsy-proven sarcoidosis when used in combination with appropriate chest imaging.

Optic Neuritis Associated with Adalimumab in the Treatment of Uveitis

Background: Tumor necrosis factor (TNF) inhibitors such as adalimumab are increasingly used in the treatment of ocular inflammatory disease refractory to standard therapies. There is evidence that TNF inhibitors are associated with demyelinating neurologic events. Objective: The authors report a case of optic neuritis and multiple sclerosis developing in association with the use of adalimumab for the treatment of bilateral chronic granulomatous iridocyclitis and multifocal choroiditis. They also review the available literature on cases of optic neuritis occurring in the setting of TNF inhibition. Results: The authors identified 21 cases of optic neuritis associated with TNF inhibition; 36% of cases with available MRI results had evidence of other demyelinating lesions in the CNS. Conclusions: The strong association between TNF inhibitors and CNS demyelination may represent an adverse effect of these drugs. Ophthalmologists should recognize the relationship between TNF inhibitors and demyelinating disease, as it can present initially with visual symptoms.

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate

Self‐referencing H+‐selective microelectrodes were used to measure extracellular H+ fluxes from horizontal cells isolated from the skate retina. A standing H+ flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H+ flux was reduced by removal of extracellular sodium or application of 5‐(N‐ethyl‐N‐isopropyl) amiloride (EIPA), suggesting activity of a Na+–H+ exchanger. Glutamate decreased H+ flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate‐induced alterations in H+ flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP‐EGTA also altered extracellular H+ flux. Immunocytochemical localization of the plasmalemma Ca2+–H+‐ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H+ flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca2+–H+‐ATPase. These neurotransmitter‐induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre‐surround receptive fields of retinal neurones.

Correlation between clinical signs and optical coherence tomography with enhanced depth imaging findings in patients with birdshot chorioretinopathy.

IMPORTANCE Birdshot chorioretinopathy (BCR) is a bilateral posterior uveitis that typically requires aggressive therapy to prevent loss of vision. Clinical signs of disease activity may be subtle and visual acuity is often preserved despite significant loss of visual function. Optical coherence tomography with enhanced depth imaging (OCT-EDI), a new technology that allows visualization of structures posterior to the retinal pigment epithelium, may be a useful tool to monitor disease activity in these patients. OBJECTIVE To determine the correlation between symptoms and signs of disease activity in BCR and specific findings on OCT-EDI. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review of 14 patients treated for BCR in the uveitis clinic at Northwestern University. All patients underwent OCT-EDI (58 scans). Clinical symptoms of photopsias/vibrating vision and signs of macular edema, vitreous haze, and retinal vasculitis were graded; a second grading scale was developed for the evaluation of OCT-EDI. Individual scans of each eye of each patient at each point were graded in a masked fashion. EXPOSURE Optical coherence tomography with EDI in BCR. MAIN OUTCOMES AND MEASURES Spearman rank correlation of clinical measures to OCT-EDI measures. RESULTS The most frequent score in each clinical category was 0 (inactive). In those BCR patients with symptoms (21 eye examinations), the subjective complaint of photopsias/vibrating vision was associated with the objective finding of suprachoroidal fluid on OCT-EDI (P = .003), and the frequency and severity of photopsias correlated with the thickness of the fluid band (Pearson product moment correlation, 0.39). Two of the clinical markers of disease activity measured in this study (vasculitis and vitreous haze) also showed a significant Spearman rank correlation with the presence and amount of suprachoroidal fluid on OCT-EDI (vasculitis, 0.45 [P < .001]; vitreous haze, 0.59 [P < .001]). CONCLUSIONS AND RELEVANCE The presence of suprachoroidal fluid on OCT-EDI appears to correlate with the subjective complaints of photopsias in patients with BCR and other more easily assessed clinical features such as vasculitis and vitreous haze. Optical coherence tomography with EDI may be a useful tool for objective monitoring of BCR.

Presentation and outcome of patients with punctate inner choroidopathy at a tertiary referral center.

Purpose: To describe the clinical course of patients with punctate inner choroidopathy seen at the University of Illinois, with emphasis on development of choroidal neovascularization (CNV). Methods: Patients with a diagnosis of punctate inner choroidopathy were identified retrospectively. The diagnosis was made clinically based on findings of multiple, small “punched-out” lesions in the posterior pole without intraocular inflammation. Medical records were evaluated for evidence of CNV. Results: Twelve patients with a diagnosis of punctate inner choroidopathy were identified. Average age at presentation was 32 years (range, 24-52 years). Eleven were women, and 11 were white. Eleven patients had available refractive data: 10 were myopic. Eight had CNV at initial presentation, and 1 later developed CNV. Eight had follow-up averaging 4 years (range, 1.4-9.6 years). Of these, five had CNV at initial presentation, and five developed new CNV. Four had multiple CNV membranes. All 6 patients with follow-up of ≥3 years had visual acuity at 3 years postpresentation of >20/40 in at least 1 eye. Four had visual acuity >20/40 bilaterally. Conclusion: Of punctate inner choroidopathy patients in this series, 75% had CNV, and more than 30% developed multiple neovascular membranes. With treatment, all patients with follow-up of ≥3 years had >20/40 vision in at least 1 eye.

Subretinal fluid in acute posterior multifocal placoid pigment epitheliopathy

Purpose: The purpose of this study was to describe the clinical finding of macular subretinal fluid by optical coherence tomography in patients with acute posterior multifocal placoid pigment epitheliopathy. Methods: Patients with acute posterior multifocal placoid pigment epitheliopathy were identified, and those with macular serous retinal detachment noted clinically and confirmed by optical coherence tomography are described. Results: Of 8 patients with acute posterior multifocal placoid pigment epitheliopathy evaluated by the uveitis service at the Illinois Eye and Ear Infirmary between 2003 and 2008, 4 eyes of 3 patients presented with macular subretinal fluid. Confirmatory optical coherence tomography was performed in two patients. Conclusion: Acute posterior multifocal placoid pigment epitheliopathy may present clinically with macular subretinal fluid. This finding can be confirmed and monitored with optical coherence tomography.

Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.

Purpose: The purpose of this study was to determine the effect on intraocular pressure (IOP) and visual acuity of treating uveitis-related hypotony in patients with vitrectomy and intravitreal silicone oil injection. Methods: Patients who underwent pars plana vitrectomy and silicone oil injection for uveitis-associated hypotony treatment were identified retrospectively. The primary outcome was maintaining an IOP of ≥5 mmHg. Visual acuity improvement was defined as an increase in ≥2 lines of acuity. Results: Twelve eyes of 10 patients were identified. Median preoperative IOP was 2 mmHg (range: 0–7 mmHg). Two of 12 eyes had an IOP of ≥5 mmHg at presentation. The number of eyes with an IOP of ≥5 mmHg was 7 of 12 eyes (58%) at 1 month, 4 of 12 eyes (33%) at 3 months, 6 of 12 eyes (50%) at 6 months, and 3 of 9 eyes (33%) at 1 year. Five of 12 eyes (42%) were reinjected between 1 and 3 times with silicone oil for recurring hypotony. Median presenting Snellen visual acuity was counting fingers (range: 20/125 to light perception). Seven of 9 eyes (78%) maintained their preoperative vision at 1 year. Conclusion: Intraocular pressure elevated modestly in most patients in this series. However, results were often transient, and some eyes required repeated silicone oil injections. Although silicone oil is reasonable to consider for the treatment and maintenance of IOP in patients with ocular hypotony secondary to uveitis, better treatments are needed.

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.

Sarcoidosis in the National Veteran Population: Association of Ocular Inflammation and Mortality

PURPOSE To describe the distribution of ocular sarcoidosis in the veteran population and to determine the association between ocular disease and all-cause mortality. DESIGN Retrospective review. METHODS The Veterans Health Administration National Patient Care Database information on medical diagnoses, date of diagnosis, age, race, gender, and Veterans Administration medical center station number for site-specific calculations for fiscal years 2010 through 2012 was collected. Mortality data were obtained from the Beneficiary Identification Records Locator Subsystem. The patient cohort was identified with a primary diagnosis of sarcoidosis using International Classification of Disease, ninth edition, code of 135 in outpatient treatment files for the study period. The sarcoidosis patients were divided into those with uveitis or orbital inflammation (defined as ocular inflammation for this study) and those without uveitis or orbital inflammation. Survival analysis was performed using the Cox proportional hazard method. MAIN OUTCOME MEASURE Association between ocular inflammation and 1-year mortality. RESULTS Of 15 130 subjects with sarcoidosis, 3364 (22.2%) were evaluated in an eye clinic within a Veterans Administration Medical Center. Most patients were diagnosed with anterior uveitis (n = 1013; 80.7% of ocular inflammation), and the least common diagnosis was orbital granuloma (n = 28; 2.2% of ocular inflammation). Male gender was protective to the development of uveitis (estimate, 0.76; 95% confidence interval, 0.65-0.88; P = 0.0005). The overall 1-year all-cause mortality for all patients with a diagnosis of sarcoidosis was 2.0%. Ocular inflammation was associated with a decrease in 1-year all-cause mortality (simple model: hazard ratio, 0.36; P = 0.0015; complex model: hazard ratio, 0.35; P = 0.013). CONCLUSIONS Veterans with ocular inflammation had significantly lower 1-year all-cause mortality than those without documented ocular inflammation. The reason for this finding remains to be established.