Debra A. Goldstein

Ocular complications of topical, peri-ocular, and systemic corticosteroids.

Topical ophthalmic, oral, and intravenous corticosteroids have long been associated with ocular side effects. Recent data suggest that inhaled corticosteroids are also associated with the development of cataract and increased intraocular pressure. Thus far, nasally administered steroids have not been associated with the same effects. Local injection of steroids, even at sites far from the eye, have been associated with the development of cataract, glaucoma, and even retinal and choroidal emboli. Any physician prescribing corticosteroids should be aware of these potential ocular side effects and should advise patients accordingly.

Epidemiology and Course of Disease in Childhood Uveitis

PURPOSE To describe the disease characteristics and visual outcome of pediatric uveitis. DESIGN Retrospective, longitudinal observation. PARTICIPANTS Five hundred twenty-seven pediatric uveitis patients from the National Eye Institute, University of Illinois, Chicago, and Oregon Health Sciences University. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Demographics, uveitis disease characteristics, complications, treatments, and visual outcomes were determined at baseline and at 1-, 3-, 5-, and 10-year time points. RESULTS The patient population was 54% female; 62.4% white, 12.5% black, 2.7% Asian, 2.1% multiracial, and 14.61% Hispanic. Median age at diagnosis was 9.4 years. The leading diagnoses were idiopathic uveitis (28.8%), juvenile idiopathic arthritis-associated uveitis (20.9%), and pars planitis (17.1%). Insidious onset (58%) and persistent duration (75.3%) were most common. Anterior uveitis was predominant (44.6%). Complications were frequent, and cystoid macular edema (odds ratio [OR] 2.94; P = 0.006) and hypotony (OR, 4.54; P = 0.026) had the most significant visual impact. Ocular surgery was performed in 18.9% of patients. The prevalence of legal blindness was 9.23% at baseline, 6.52% at 1 year, 3.17% at 3 years, 15.15% at 5 years, and 7.69% at 10 years. Posterior uveitis and panuveitis had more severe vision loss. Hispanic ethnicity was associated with a higher prevalence of infectious uveitis and vision loss at baseline. CONCLUSIONS The rate and spectrum of vision threatening complications of pediatric uveitis are significant. Prospective studies using standard outcome measures and including diverse populations are needed to identify children most at risk.

Long-term follow-up of patients treated with short-term high-dose chlorambucil for sight-threatening ocular inflammation.

PURPOSE To determine the effectiveness of short-term high-dose chlorambucil in the treatment of sight-threatening uveitis and to ascertain the incidence of severe side effects, particularly late malignancy. DESIGN Retrospective, noncomparative interventional case series. PARTICIPANTS Fifty-three patients treated at the University of Illinois at Chicago Eye and Ear Infirmary and the private office of one of the authors for severe sight-threatening uveitis. METHODS Treatment with short-term high-dose chlorambucil (2-9 months of therapy). MAIN OUTCOME MEASURE Visual acuity and degree of inflammation were assessed at every visit. The development of systemic side effects, including malignancy, was assessed using a detailed questionnaire. RESULTS Total cumulative dose of chlorambucil ranged from 392 to 5200 mg with an average of 1429 mg. The maximum daily dose ranged from 10 to 30 mg with an average of 20 mg. Average duration of treatment was 16 weeks with a range of 7 to 40 weeks. Seventy-seven percent of patients treated were in remission with an average follow-up of 4 years (range: 6 months to 24 years). Forty-seven percent had at least two lines of improvement in Snellen visual acuity after treatment, with an average gain of 3.5 lines. Adverse effects include secondary amenorrhea, nonophthalmic herpes zoster, testicular atrophy, and erectile dysfunction. None of the patients had developed a malignancy as of their last follow-up. CONCLUSION Short-term high-dose chlorambucil therapy may be a reasonable option in patients with intractable sight-threatening uveitis.

Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging.

Purpose: To report the structural and functional changes in acute macular neuroretinopathy (AMN) and their long-term evolution. Multimodal retinal imaging was acquired, including Fourier domain optical coherence tomography (OCT), infrared (IR) reflectance, and near IR autofluorescence (NIA). Methods: In this retrospective observational case series, detailed clinical history and multimodal imaging are reported in eight patients with AMN. Manual segmentation of the Fourier domain OCT volume scans was done in one patient with the largest AMN lesion to yield retinal sublayer topographic maps. Results: Two patients were seen within the first 1 to 2 days of symptoms, and both showed outer nuclear and outer plexiform layer hyperreflectivity. Both patients developed enlargement of the lesion over the first week on IR reflectance imaging with a corresponding lateral extension of the outer retinal disruption on Fourier domain OCT. Thinning of the outer nuclear layer persisted in all patients with lesions >100 &mgr;m width, and in one patient this thinning worsened over the course of follow-up, as noted on the sublayer maps. This structural abnormality correlated with long-term functional deficits, persisting up to 14 months after the initial episode. Infrared reflectance highlights the lesion best, and abnormalities on near IR autofluorescence may be present. Conclusion: Acute macular neuroretinopathy acutely affects the outer nuclear and plexiform layers manifesting as OCT hyperreflectivity. The hallmark long-term changes are outer nuclear thinning on Fourier domain OCT and a fading dark lesion on IR reflectance imaging. These changes correspond to focal disruption of the outer segment/retinal pigment epithelium junction on OCT, and not the inner segment/outer segment junction, as previously reported. Optical coherence tomography and near IR autofluorescence abnormalities suggest previously unrecognized melanin and retinal pigment epithelium derangements in this condition.

Adalimumab therapy for refractory uveitis: results of a multicentre, open-label, prospective trial

Objective Tumour necrosis factor (TNF) blockers have been demonstrated to be effective in the treatment of systemic and ocular inflammatory diseases. We conducted a prospective, multicentre, open-label Phase II clinical trial to assess the effectiveness and safety of adalimumab, a fully human anti-TNF monoclonal antibody, in treating refractory uveitis. Methods Subjects with non-infectious uveitis refractory to corticosteroids and at least one other immunosuppressive medication were enrolled. Treatment outcome was ascertained by a composite endpoint comprised of visual acuity, intraocular inflammation, ability to taper immunosuppressives, and posterior segment imaging. Clinical response was defined by improvement in at least one parameter, worsening in none, and well controlled intraocular inflammation. Week 10 responders were permitted to continue receiving adalimumab for the study duration of 50 weeks. Results Twenty-one of 31 patients (68%) were characterised as clinical responders at 10 weeks, of whom 12 patients (39%) exhibited durable response after 50 weeks. The most common reason for study termination was primary or secondary inefficacy. No patients experienced treatment-limiting toxicity clearly related to study therapy. Conclusions Adalimumab was safe and effective in 68% of refractory uveitis patients 10 weeks after study enrolment, and maintained in 39% after 1 year. Ongoing study is required to determine the place of adalimumab and other TNF blockers in the treatment of uveitis.

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.

Long-term follow-up of acute retinal necrosis

Purpose: The purpose of this study was to report long-term visual outcome of acute retinal necrosis. Methods: Medical records of patients with acute retinal necrosis were reviewed. Results: Thirty-two patients were diagnosed with acute retinal necrosis from 1998 to 2007. Twenty patients (25 eyes) had at least 1 follow-up and available medical records. Intravitreal injections of ganciclovir and/or foscarnet were administered in 11 of 25 eyes. Intravenous and oral antiviral medications were used in 14 of 20 and 19 of 20 patients, respectively. Eleven of 25 eyes had <25% of retina affected, 8 of 25 had 25% to 50% of retina affected, and 6 of 25 had >50% of retina affected. Mean visual acuity at all time points was best when retinitis involved <25% and decreased as area increased. All but 1 eye with >50% involvement experienced decreased vision regardless of treatment. Three of 4 eyes with 25% to 50% involvement that received intravitreal antivirals had an improvement in visual acuity of ≥2 Snellen lines. Five of 25 eyes developed retinal detachment. None of the six eyes treated with prophylactic laser detached. Conclusion: Greater extent of retinitis portends a worse visual prognosis. Although intravitreal treatment did not prevent visual acuity loss in patients with severe disease, patients with moderate disease (25-50% retina involved) did well with intravitreal therapy with most having stable or improved visual acuity. Prophylactic laser decreased the rate of detachment.

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.

Mycobacterial ocular inflammation: delay in diagnosis and other factors impacting morbidity.

IMPORTANCE The reported outcomes of ocular mycobacterial infection are commonly unfavorable. This study is among the first to elucidate factors associated with poor outcomes, as well as highlight the continued controversies in therapy, particularly the role of oral corticosteroids. OBJECTIVE To describe presentations and outcomes of mycobacterial ocular disease in the Midwestern United States. DESIGN Retrospective case series. SETTING A university-based uveitis clinic. PARTICIPANTS Twenty-six eyes of 17 patients with mycobacterial ocular inflammatory disease seen at University of Illinois at Chicago from 1995 to 2010. MAIN OUTCOME MEASURES Bivariate and regression analyses were performed to assess factors associated with delay in referral, relapse, and irreversible visual acuity loss (≤ 20/200). RESULTS Of 17 patients, 13 had isolated ocular disease, 1 had miliary tuberculosis (TB), 2 had TB lymphadenopathy, and 1 had active pulmonary TB. Fourteen had Mycobacterium tuberculosis and 3 had nontuberculous mycobacterial infection. Chest imaging was consistent with granulomatous disease in 46.7%. Average delay from ocular disease onset to uveitis service referral was 755.3 days. Posterior uveitis and non-Hispanic white race were associated with increased delay. A relapsing course was observed in posterior uveitis (odds ratio [OR], 20.0; 95% CI, 1.39-287; P = .03) and those treated with systemic steroids for eye disease (OR, 10.1; 95% CI,1.60-64.0; P = .01). Disease control was achieved in 81%, although 38.5% had profound visual loss, associated with age older than 50 years and delay in diagnosis. Patients diagnosed after 500 days from initial ocular symptoms were more likely to lose vision (OR, 20.0; 95% CI, 1.41-282; P = .03). CONCLUSIONS Ocular mycobacterial infection occurs in nonendemic areas and cannot be ruled out with negative chest imaging. Tuberculosis and atypical mycobacterial infection should be in the differential diagnosis of ocular inflammation, regardless of patient ethnicity. Significant delays exist in instituting antimicrobial treatment, associated with increased morbidity. Early referral is necessary for patients not responding appropriately to anti-inflammatory therapy.