Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis.

Experimental autoimmune uveitis (EAU) induced in mice by immunization with the retinal Ag interphotoreceptor retinoid-binding protein (IRBP) is a model of human autoimmune uveitis. We examined whether T regulatory cells (Tregs) found in uveitic eyes are IRBP specific, functionally suppressive, and play a role in natural resolution of disease and in maintenance of remission. Progressive increase of Foxp3(+) Treg to T effector cell (Teff) ratio in uveitic eyes correlated with resolution of disease. At peak disease, up to 20% of Tregs (CD4(+)Foxp3(+)) and up to 60% of Teffs (CD4(+)Foxp3(-)) were IRBP specific, whereas in lymphoid organs retina-specific T cells were undetectable. Tregs isolated from eyes of mice with EAU efficiently suppressed IRBP-specific responses of Teffs from the same eyes. Importantly, systemic depletion of Tregs at peak disease delayed resolution of EAU, and their depletion after resolution triggered a relapse. This could be partially duplicated by depletion of Tregs locally within the eye. Thus, the T cell infiltrate in uveitic eyes of normal mice with a polyclonal T cell repertoire is highly enriched in IRBP-specific Tregs and Teffs. Unlike what has been reported for Tregs in other inflammatory sites, Tregs from uveitic eyes appear unimpaired functionally. Finally, Foxp3(+) Tregs play a role in the natural resolution of uveitis and in the maintenance of remission, which occurs at least in part through an effect that is local to the eye.

Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management.

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the ß globin gene resulting in the substitution of glutamic acid by valine at position 6 of the ß globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

Isolated endogenous Nocardia endophthalmitis after immunosuppression.

PURPOSE: This study is aimed to report a case of endogenous Nocardia endophthalmitis in the setting of immunosuppression from chronic steroid use. METHODS: A case report was conducted. RESULTS: A 79-year-old woman presented with decreased vision with floaters in the left eye. Ophthalmic examination revealed severe inflammation in the anterior chamber, vitreous opacities, and retinal detachment. Vitreous cultures grew Nocardia farcinica without any systemic foci of infection found during further workup. The patient was treated with intravitreal amikacin and oral trimethoprim-sulfamethoxazole, and her retinal detachment was later repaired in the operating room. The patient has since remained stable with no signs of retinal detachment or active infection. CONCLUSIONS: Nocardia endophthalmitis is a rare, but serious intraocular infection that should be considered in the differential diagnosis in any immunosuppressed patient, including those receiving steroids, who presents with signs of intraocular infection.

Spectral-Domain OPTICAL COHERENCE TOMOGRAPHY of a Macular Fold AFTER Retinal Detachment Repair.

PURPOSE: We report a case with a dry macular fold after retinal detachment repair using spectral-domain optical coherence tomography images (SD-OCT) to evaluate details of the retinal architecture before and after surgical management. METHODS: A 62-year-old man diagnosed with macula-threatening rhegmatogenous retinal detachment underwent primary vitrectomy with an encircling sclera buckle. On post-operative day 5, he was noted to have developed a juxtafoveal retinal fold. SD-OCT was used to image the retinal fold and documented apposition of the retinal layers and discontinuity within the photoreceptor layer in the vicinity of the retinal fold. RESULTS: The attempts to detach and unfold the retina appeared minimally successful intraoperatively. However, as the gas bubble decreased, the retinal fold was noted to have resolved. Repeat SD-OCT documented flattening of the retinal fold with a well-preserved photoreceptor layer. CONCLUSION: This outcome suggests the possibility of delayed postoperative success in flattening a retinal fold despite resistance to manipulation and failed attempts during the course of the surgery. To our knowledge, this is the first report that demonstrates this finding within the macular architecture after retinal detachment surgery in vivo using spectral-domain optical coherence tomography. These findings may have an important role in management of these cases and may become prognostic indicators based on the alterations in retinal anatomy demonstrated by high-resolution 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 > or =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.

Sympathetic ophthalmia: incidence of ocular complications and vision loss in the sympathizing eye.

PURPOSE: To report the frequency on presentation and subsequent incidence of ocular complications and vision loss in patients with sympathetic ophthalmia (SO) and to describe factors associated with decreased vision in the sympathizing eye. DESIGN: Multicenter retrospective case series. SETTING: Three academic tertiary care uveitis clinics. STUDY POPULATION: Eighty-five patients with SO from 1976 to 2006. OBSERVATION PROCEDURES: Review of existing medical records. MAIN OUTCOME MEASURES: Incident visual acuity (VA) loss to 20/50 or worse and 20/200 or worse and the median acuity over time. RESULTS: Twenty-six percent of patients with SO presented with a VA of 20/200 or worse in their sympathizing eye. Further development of vision loss to 20/200 or worse occurred at the rate of 10% per person-year (PY). Ocular complications were seen in the sympathizing eye in 47% of patients at presentation; further development of new complications occurred at the rate of 40%/PY. The ocular complications most often associated with decreased vision were cataract and optic nerve abnormality. Exudative retinal detachment and active intraocular inflammation were significantly associated with poorer VA in the sympathizing eye. The benefits of corticosteroids were indirectly demonstrated as their use led to more rapid disease inactivation. Fifty-nine percent of patients maintained a VA of better than 20/50 in their sympathizing eye; and 75% maintained a VA of better than 20/200. CONCLUSIONS: Although ocular complications were seen in many sympathizing eyes with SO, most patients maintained functional VA. The presence of an exudative retinal detachment and active intraocular inflammation correlated with poorer vision in the sympathizing eye.

Uveitis associated with pediatric behçet disease in the american midwest.

PURPOSE: To describe demographics, clinical course, treatment, and visual prognosis of uveitis in pediatric patients with Behçet disease, and to compare childhood-onset with adult-onset Behçet uveitis. DESIGN: Retrospective, observational case series. METHODS: setting: Uveitis service, University of Illinois at Chicago and private office of one of the authors (H.H.T.). study population: Patients diagnosed with Behçet uveitis using International Study Group criteria between January 1, 1973 to December 31, 2007. main outcome measures: Demographics, symptoms, clinical course, management, laboratory tests, complications, and visual prognoses were recorded. RESULTS: Thirty-three patients had available records with at least one month follow-up; four were children and 29 were adults. All children and 19 adults were male. The most common initial symptom was oral ulcers and the most common uveitis type was panuveitis with retinal vasculitis in both groups. There was an average delay of one year among children and 1.8 years among adults between onset of uveitis and disease diagnosis. Immunosuppressive therapy was employed in all children and 23 of 29 adults. Treatment response was variable in both groups. Maculopathy was the most common cause of permanent visual impairment, both in children and in adults. Six of eight pediatric eyes (75%) and 13 of 25 adult eyes (52%) retained a visual acuity better than 20/200 at three years. CONCLUSIONS: Behçet disease is an uncommon cause of uveitis in the United States, with a male predominance. Although the clinical picture of Behçet uveitis was similar among both groups, the visual prognosis appeared worse in adults. Awareness of this disease should be increased in nonendemic areas to prevent blindness resulting from delays in diagnosis.

The Heidelberg Retina Tomograph vs clinical impression in the diagnosis of glaucoma.

PURPOSE: To compare the sensitivity and the specificity of the Heidelberg Retina Tomograph (HRT) classification of "Glaucoma" or "Normal" with that derived from clinical impression (CI) based on several parameters. DESIGN: Consecutive observational case series. METHODS: In a retrospective chart review of 200 left eyes of 200 consecutive patients referred to the Glaucoma Service Diagnostic Laboratory of the Wills Eye Hospital, we compared the HRT-based classification of "Glaucoma" or "Normal" with a CI classification of "Definite glaucoma," "Probably glaucoma," "Probably no glaucoma," and "No glaucoma." RESULTS: The HRT-based diagnosis of "Glaucoma" or "Normal" had an 86% sensitivity and 68% specificity when compared with a clinical impression (CI) of "Definite glaucoma," used as a strict gold standard definition of glaucoma; an 83% sensitivity and 57% specificity when the CI "Definite glaucoma" and "Probably glaucoma" were combined as a more liberal definition of glaucoma; a 76% sensitivity and 69% specificity when the CI "Definite glaucoma," "Probably glaucoma," and "Probably no glaucoma" were combined as the most liberal definition of glaucoma. The HRT diagnosis had an 86% sensitivity and 51% specificity when compared with the groups "Probably glaucoma," "Probably no glaucoma," and "No glaucoma" combined and considered as no glaucoma. CONCLUSIONS: In this study, HRT-based classification of "Glaucoma" or "Normal" was moderately sensitive, but not very specific when compared with the clinical impression as the gold standard. Clinicians should not rely on the HRT diagnosis alone, but should use it to supplement the impression based on an eye examination and other ancillary tests.