Robert C. Wang

A prospective evaluation of subconjunctival injection of triamcinolone acetonide for resistant anterior scleritis.

PURPOSE Prospective evaluation of the efficacy and safety of subconjunctival triamcinolone injections for resistant, nonnecrotizing, anterior scleritis. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Twelve eyes of 10 consecutive patients seen in the Doheny Eye Institute between August 1999 and December 2000 with diffuse, nonnecrotizing anterior scleritis that was resistant to systemic antiinflammatory therapy. Eyes with a history of steroid response were excluded. INTERVENTION Subconjunctival injection of triamcinolone acetonide to the areas of maximal inflammation. MAIN OUTCOME MEASURES Scleritis activity, adverse treatment effects, and number of systemic medications required at the end of the follow-up period. RESULTS Within 1 to 14 days after injection, complete resolution of signs and symptoms was achieved in 11 eyes and partial resolution in 1 eye. Two patients had one recurrence each, 2.5 and 11 months after injection. Six of 10 patients were able to discontinue all systemic therapy (prednisone +/- immunosuppressive drugs); the remaining 4 needed continued oral therapy for systemic indications. Transient ocular hypertension and subconjunctival hemorrhage occurred in one eye each. Median follow-up period was 15 months. No eye developed necrotizing scleritis. CONCLUSIONS Subconjunctival injection of triamcinolone acetonide is a safe and effective treatment for resistant, nonnecrotizing anterior scleritis. It provides rapid effect, is well tolerated, and may spare patients the significant complications and side effects of systemic corticosteroid and immunosuppressive therapy.

Associations among Visual Acuity and Vision- and Health-Related Quality of Life among Patients in the Multicenter Uveitis Steroid Treatment Trial

PURPOSE To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis. METHODS Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL. RESULTS Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29-0.52). CONCLUSIONS The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost-utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.).

Long-Term, Multicenter Evaluation of Subconjunctival Injection of Triamcinolone for Non-Necrotizing, Noninfectious Anterior Scleritis

PURPOSE We sought to characterize the long-term outcomes and complications of subconjunctival triamcinolone acetonide injection (STI) for non-necrotizing, noninfectious anterior scleritis. DESIGN Retrospective, interventional, noncomparative, multicenter study. PARTICIPANTS Sixty-eight eyes of 53 patients from 9 participating hospitals in the United States, Singapore, and Australia. Only eyes with 6 or more months of follow-up were included. INTERVENTION Subconjunctival injection of 2 to 8 mg of triamcinolone acetonide was administered to eyes with non-necrotizing, noninfectious anterior scleritis. MAIN OUTCOME MEASURES Resolution of signs and symptoms, time to recurrence of scleritis, and side effect profile. RESULTS Median follow-up was 2.3 years (range, 6 months to 8.3 years). Sixty-six eyes (97.0%) experienced improvement of signs and symptoms after 1 injection. Twenty-four months after a single injection, 67.6% of eyes remained recurrence-free, whereas at 48 months, 50.2% were recurrence-free. Some 55.0% of patients who had adverse effects from systemic medications were off all systemic medications at last follow-up; 55.0% of patients who were taking systemic medications at the time of first triamcinolone acetonide injection were not taking prednisone and immunosuppressants at this time; 76.2% of patients still requiring systemic agents had associated systemic disease. Fourteen eyes (20.6%) had ocular hypertension not requiring intraocular pressure (IOP)-lowering therapy. Two eyes (2.9%) were treated with topical IOP-lowering agents alone, and 2 eyes required surgical intervention for glaucoma. None developed scleral necrosis or melt. CONCLUSIONS This retrospective, international study carried out at 9 hospitals suggests that STI can treat non-necrotizing, noninfectious anterior scleritis with side effects limited to elevated IOP in a few patients. Although no cases of scleral melt or necrosis were observed, we cannot definitively conclude that this may not occur after STI. Intraocular pressure should be closely monitored after STI. Subconjunctival triamcinolone acetonide injection may be useful as adjuvant therapy or to decrease systemic medication burden. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Massive mycobacterial choroiditis during highly active antiretroviral therapy: another immune-recovery uveitis?

PURPOSE To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). STUDY DESIGN Case report and literature review. PARTICIPANTS A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. METHODS The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). RESULTS Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. CONCLUSIONS This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

Microglial stability and repopulation in the retina.

Background/aims: Parenchymal central nervous system microglia are repopulated by bone marrow derived monocytes more slowly than any other reticuloendothelial cells. The contribution of bone marrow derived monocytes to the uninflammed retina has not been studied. The present study sought to determine repopulation of retinal microglia in uniflammed retina by bone marrow derived monocytes in bone marrow chimeric rats. Methods: Chimeric (Y→X) Lewis rats were constructed by transplanting 5×107 male bone marrow cells into lethally irradiated female recipient rats. The chimeras were sacrificed 8, 10, 12, 30, and 52 weeks after bone marrow transplant, and retina, brain, lung, and spleen samples were collected. DNA was extracted and quantified. Y positive infiltrating cells in the collected samples were detected by polymerase chain reaction amplification of a Y chromosome specific 104 bp fragment. Results: There was a rapid repopulation of haematopoietic tissues in the spleen (at 8 weeks), confirming the establishment of chimerism, and to a lesser extent, of lung (at 30 weeks). This repopulation was absent in the brain parenchyma and retina until 52 weeks after transplantation. Conclusions: These data indicate that resident microglia in the retina, much like those in the brain, are stable in number in the retinal compartment (up to 1 year), and repopulation by bone marrow derived cells may be delayed for a year.

Conjunctival ulcers in Behçet's disease

PURPOSE To describe the occurrence of conjunctival ulcers as a manifestation of Behçets disease. DESIGN Retrospective, noncomparative, interventional case series with histopathologic correlation. METHODS Six patients who fulfilled the diagnostic criteria for Behçets disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin. RESULTS Although all six patients fulfilled the diagnostic criteria for Behçets disease, two developed uveitis and other signs of Behçets disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring. CONCLUSIONS In addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behçets disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behçets disease.

Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a clinicopathologic study.

Juvenile xanthogranuloma (JXG) is a rare, pediatric histiocytic skin disorder that may affect the eye. It can present with protean ocular manifestations, including masquerade uveitis, heterochromia, hyphema, or glaucoma. It very rarely involves the retina and posterior segment; indeed, posterior involvement has been documented histopathologically in only one case. We present the case of a 2-year-old child with ocular JXG presenting as chronic, refractive uveitis, without skin or systemic findings. The blind, painful eye was enucleated and found to harbor a diffuse histiocytic process that involved both the anterior and posterior segments, including the retina and subretinal space. Histological, immunohistochemical, and electron microscopic studies confirmed the diagnosis of JXG. The pathologic classification and differential diagnosis of systemic histiocytic disorders are discussed. Since JXG can present as masquerade pediatric uveitis, this entity should be considered in children with atypical uveitis. In rare instances, JXG may involve the posterior segment and the retina, leading to retinal detachment and blindness.

Article for CME creditMassive mycobacterial choroiditis during highly active antiretroviral therapy: Another immune-recovery uveitis?☆

PURPOSE To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). STUDY DESIGN Case report and literature review. PARTICIPANTS A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. METHODS The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). RESULTS Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. CONCLUSIONS This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature

Abstract Purpose: To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods: Retrospective case series and comprehensive literature review. Results: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25–13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.

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.