Alejandro Rodriguez

Outcomes in anterior uveitis associated with the HLA-B27 haplotype

OBJECTIVE This study aimed to test the hypothesis that patients presenting with anterior uveitis who are HLA-B27 positive, either with or without associated systemic disease, have a less-favorable outcome than do patients with idiopathic anterior uveitis who are HLA-B27 negative. DESIGN Retrospective case-controlled series. PARTICIPANTS Ninety-seven patients who were HLA-B27 positive with no systemic disease, 94 patients who were HLA-B27 positive with systemic disease, and 72 patients who were HLA-B27 negative who presented with anterior uveitis were studied. MAIN OUTCOME MEASURES Ocular complications (e.g., secondary glaucoma, cataract formation, pupillary synechiae, vitritis, cystoid macular edema, and optic disc edema), medical and surgical treatment, number of recurrent attacks, and final visual acuity were recorded for all patients. RESULTS The patients who were HLA-B27 positive, either with or without systemic disease, experienced a greater number of complications than did the patients who were HLA-B27 negative. Periocular corticosteroids, systemic corticosteroids, and systemic immunosuppressive chemotherapy were required in a far greater number of HLA-B27-positive patients than in HLA-B27-negative patients (60% vs. 11%, 53% vs. 7%, and 18% vs. 1%, respectively; P < 0.001). The percentage of legally blind eyes was significantly greater in the HLA-B27-positive group, both with and without systemic disease, when compared with the HLA-B27-negative group (11% vs. 2%; P < 0.005). CONCLUSIONS The prognosis of anterior uveitis associated with the HLA-B27 haplotype, either with or without associated systemic disease, is less favorable when compared with that of HLA-B27-negative patients with idiopathic anterior uveitis.

Secondary Glaucoma in Patients with Uveitis

Purpose: To evaluate the prevalence of secondary glaucoma (SG), clinical forms of uveitis more frequently associated with glaucoma, and describe the treatment and complications encountered in a cohort of patients with glaucoma and uveitis during a 10-year period. Methods: The hospital records of patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary for a decade were reviewed for cases of SG. Results: One hundred and twenty of the 1,254 patients (9.6%) with uveitis developed SG. SG was more frequent in anterior uveitis (67%) but was also associated with posterior uveitis (13%) and pars planitis (4%). Herpetic keratouveitis (22%), Fuchs’ iridocyclitis (19%), juvenile rheumatoid arthritis-associated iridocyclitis (16%), syphilis (14%), and sarcoidosis (12%) were the leading types of uveitis associated with SG. Despite aggressive medical and surgical therapy, SG was associated with progressive visual field loss and optic nerve damage in 39 patients (33%). Conclusion: SG is an underappreciated, vision-threatening complication in patients with uveitis. Increased vigilance for emergence of this complicating problem during the care of patients with uveitis is warranted, and medical and surgical treatment for reducing IOP should be especially aggressive in these patients. We hypothesize that earlier, more aggressive treatment of uveitis will reduce the presence of glaucoma as an additional vision-robbing complication of uveitis.

Posterior Segment Ocular Manifestations in Patients with HLA-B27—associated Uveitis

PURPOSE To describe a series of patients with seronegative arthritic syndromes and HLA-B27-associated uveitis with severe, sight-threatening, posterior segment ocular manifestations. METHODS The authors reviewed the records of 29 patients (17.4%) with posterior segment involvement from a cohort of 166 patients with HLA-B27-associated uveitis. The inclusion criteria included individuals with a positive HLA-B27 who had at least one of the following findings: (1) severe vitreous inflammation; (2) papillitis; (3) retinal vasculopathy; or (4) pars plana exudates. The study population comprised 13 men and 16 women with a mean age at onset of uveitis of 35.2 years. The average duration of the uveitis was 5.3 years, and the median follow-up time was 26 months. FINDINGS Posterior segment involvement occurred in 34 eyes of the 29 patients. The most common findings included severe and diffuse vitritis in 93.1% of the patients and papillitis in 24 patients (82.7%). Retinal vasculitis occurred in seven patients (24.1%), and pars plana exudates were present in two patients (6.8%). Cystoid macular edema (37.9%) and epiretinal membrane (17.2%) were common causes of visual impairment. Systemic immunosuppressive therapy was required for control of inflammation in 32% of the patients. CONCLUSION HLA-B27-associated uveitis may be related to severe, sight-threatening posterior segment manifestations in some patients; this is an under-recognized phenomenon. These patients may require the use of aggressive systemic immunosuppressive therapy to control inflammation and preserve vision.

Low-dose Cyclosporine Therapy in the Treatment of Birdshot Retinochoroidopathy

INTRODUCTION Birdshot retinochoroidopathy is an uncommon uveitic syndrome of presumed autoimmune etiology. Therapy with systemic and periocular steroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Steroid-sparing strategies with more specific agents such as cyclosporine (Cyclosporin A, CSA) have been suggested as the first line treatment for this disease. PATIENTS AND METHODS The records of 19 patients (35 eyes) with the clinical diagnosis of birdshot retinochoroidopathy were examined. Age at onset ranged from 33 to 69 years (mean, 46.1 years) in nine men and ten women. The median follow-up from disease onset was 36 months. Eight patients were treated with low-dose (2.5-5 mg/kg daily) CSA alone, six required the addition of azathioprine (1.5-2 mg/kg daily), and six received no systemic immunosuppressive therapy. RESULTS HLA-A29 was positive in 94% (16 of 17) of patients tested. Vitreous inflammation was controlled in 23 (88.5%) treated eyes, with fewer bouts of recurrent inflammation, and a corresponding improvement or stabilization of visual acuity in 20 (83.3%) eyes. In contrast, intraocular inflammation never was controlled fully in untreated eyes, and visual acuity decreased in six (54.5%) eyes by an average of 2.5 Snellen lines. Nephrotoxic side effects of low-dose CSA therapy were not observed, but hypertension developed in two patients. CONCLUSION Although the definitive strategy for the management of birdshot retinochoroidopathy is unknown, control of intraocular inflammation with a favorable visual outcome, together with a lack of demonstrable CSA-associated nephrotoxicity and secondary side effects in these patients with birdshot retinochoroidopathy indicate that vision preservation is possible with low-dose CSA alone or in combination with other steroid-sparing immunosuppressive agents as an alternative to the long-term use of corticosteroids.

Increasing the Diagnostic Yield of Conjunctival Biopsy in Patients with Suspected Ocular Cicatricia1 Pemphigoid

BACKGROUND Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition. MATERIALS AND METHODS Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed. RESULTS One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique. CONCLUSION The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid.

Ocular Rosacea: A Histologic and Immunopathologic Study

Acne rosacea is an idiopathic dermatologic disease that frequently produces conjunctival inflammation. The authors studied the histology and immunopathology of epibulbar conjunctival biopsy specimens from eight patients with ocular rosacea and compared the findings with those from conjunctiva from 13 normal individuals. The conjunctival epithelium in ocular rosacea was attenuated and infiltrated by inflammatory cells, mainly T-helper/inducer (CD4) cells, phagocytic cells, and antigen-presenting (CD14, Mac-1) cells. The difference between the normal control group and the rosacea group in the number of mononuclear cells forming these populations was statistically significant (P < 0.01). The substantia propria of the rosacea specimens contained large subepithelial infiltrates of chronic inflammatory cells, and in some cases frank granulomaformation was evident. There was an overall mean increase of nearly all cell types, but especially of T-helper cells in the rosacea specimens compared with the controls. Interestingly, T-helper/inducer (CD4) cells, which were outnumbered by the T-suppressor (CD8) cells in the normal conjunctiva) epithelium (CD4/CD8 = 0.85), outnumbered the CD8-positive cells in the rosacea specimens (CD4/CD8 = 1.6). There also was a 3.5-fold increase of the CD4/CD8 ratio in the rosacea conjunctiva) stroma compared with the normal specimens. The mechanism involved in rosacea conjunctiva) inflammation resembles a type IV hypersensitivity reaction.

Disease Relapse in Patients with Ocular Manifestations of Wegener Granulomatosis

Purpose: To evaluate possible factors associated with disease relapse in patients with ocular manifestations of Wegener granulomatosis. Methods: Eight patients with ocular manifestations of Wegener granulomatosis were longitudinally followed for a mean period of 34 months. Serial antineutrophil cytoplasmic antibody (ANCA) levels were determined on all patients. Results: All eight patients had either scleritis alone or scleritis combined with peripheral ulcerative keratitis. Clinical disease remission was achieved in all patients using immunosuppressive chemotherapy. Five patients had subsequent relapse after treatment withdrawal. The serum ANCA level had failed to revert to normal during remission in four of the five patients who had had relapses. The ANCA levels for all three patients who remained in remission without therapy converted to normal. There was no significant difference in the initial serum ANCA level ( P = 0.35) or the mean cumulative cyclophosphamide dose ( P = 0.13) between those who had a relapse and those who did not. Conclusion: Failure of ANCA titers to revert to normal levels may be associated with the potential for relapse in patients with ocular manifestations of Wegener granulomatosis.

Systemic Immunosuppressive Therapy and the Occurrence of Malignancy in Patients with Ocular Inflammatory Disease

PURPOSE To compare the occurrence of malignancy in patients with severe ocular inflammatory disease treated with systemic corticosteroids alone or with systemic immunosuppressive drugs with or without systemic corticosteroids. METHODS The clinical records of 543 patients with ocular inflammatory disease treated with systemic corticosteroids and/or immunosuppressive chemotherapy were reviewed in a retrospective cohort study. Characteristics of patients treated with corticosteroids alone were compared with characteristics of patients treated with immunosuppressive agents with or without preceding corticosteroid treatment. The rates of malignancy after initiation of drug therapy were compared using an exact test for incidence rate data. RESULTS Compared with patients treated with corticosteroids alone, patients treated with immunosuppressants with or without corticosteroid treatment were older and had more severe systemic disease. During a total of 1261 person-years of follow-up, a malignancy developed in five patients. The rate of malignancy in the immunosuppressant group (4 malignancies during 968 person-years of follow-up) was not significantly different from the rate in the corticosteroids alone group (1 malignancy during 293 person-years of follow-up) (P > 0.90, exact test for incidence rate data). CONCLUSION These findings do not support the hypothesis of an increased risk of malignancy in patients with severe ocular inflammatory disease who are treated with systemic immunosuppressive agents compared with patients treated with systemic corticosteroids.

Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600–800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19 – 78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600–800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p<0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p<0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.

Post-traumatic transient cortical blindness

Five patients: three children, one adolescent, and one young adult, examined in an emergency room setting were diagnosed with post-traumatic transient cortical blindness. This syndrome is characterized by transient visual loss, normal pupillary response and normal funduscopic examination following minor head trauma. In each case, vision returned to normal within minutes to hours following injury, leaving no neurological sequelae. Headache, confusion, irritability, anxiety, nausea and vomiting were the most common related symptoms. While the mechanism responsible for the transient blindness is unknown, most authors propose an abnormal vascular response to trauma with resultant transient hypoxia and cerebral dysfunction. The similarity between the symptoms accompanying this syndrome and those seen during a classic migraine attack has led many investigators to suggest a common underlying pathophysiology. The purpose of this report is to highlight the salient clinical features and diagnostic approaches to this syndrome, thereby providing ophthalmologists and emergency room physicians a heightened awareness of this entity and the means to detect it.