Classification Criteria for Intermediate Uveitis, Non–Pars Planitis Type

Purpose: To determine classification criteria for intermediate uveitis, non-pars planitis type (IU- NPP, also known as undifferentiated intermediate uveitis) / Design: Machine learning of cases with IU-NPP and 4 other intermediate uveitides. / Methods: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. / Results: Five hundred eighty-nine of cases of intermediate uveitides, including 114 cases of IU-NPP, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for IU-NPP included unilateral or bilateral intermediate uveitis with neither 1) snowballs in the vitreous nor 2) snowbanks on the pars plana. Other key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0 % in the training set and 0% in the validation set, respectively. / Conclusions: The criteria for IU-NPP had a low misclassification rate and appeared to perform well enough for use in clinical and translational research

Classification Criteria for Multiple Sclerosis-Associated Intermediate Uveitis

PURPOSE: The purpose of this study was to determine classification criteria for multiple sclerosis-associated intermediate uveitis. DESIGN: Machine learning of cases with multiple sclerosis-associated intermediate uveitis and 4 other intermediate uveitides. METHODS: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated in the validation set. RESULTS: A total of 589 cases of intermediate uveitides, including 112 cases of multiple sclerosis-associated intermediate uveitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval: 96.1-99.9). Key criteria for multiple sclerosis-associated intermediate uveitis included unilateral or bilateral intermediate uveitis and multiple sclerosis diagnosed by the McDonald criteria. Key exclusions included syphilis and sarcoidosis. The misclassification rates for multiple sclerosis-associated intermediate uveitis were 0 % in the training set and 0% in the validation set. CONCLUSIONS: The criteria for multiple sclerosis-associated intermediate uveitis had a low misclassification rate and appeared to perform sufficiently well enough for use in clinical and translational research

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Characterization of serous retinal detachments in uveitis patients with optical coherence tomography

To determine the prevalence of serous retinal detachments (SRD) using optical coherence tomography (OCT) in a large database of patients with uveitis from a tertiary referral setting, to describe clinical features of patients with SRD, and to ascertain retinal architectural features found in association with SRD. Main outcome measures Prevalence of SRD in uveitis patients imaged with OCT, correlation of visual acuity with SRD, anatomic subtypes of uveitis identified, and association of SRD with various subtypes of macular edema (focal and diffuse) and retinal architectural abnormalities. Design Retrospective, single-setting cross-sectional study of all OCTs in a digital imaging base ordered on patients from a tertiary referral uveitis clinic between July 2006 and March 2008. Results SRD were identified in 17 of 111 uveitis patients (15 %) reviewed; bilateral SRD were found in 5 of 17 patients (29 %). Intermediate uveitis was the most common disease association (47 %), but other conditions identified included Vogt-Koyanagi-Harada syndrome, multifocal choroiditis/panuveitis, and sarcoidosis. Retinal architectural features identified in association with SRD included focal macular edema (59 %), diffuse macular edema (50 %), any intraretinal edema (77 %), both diffuse and focal macular edema (32 %), and retinal pigment epithelial alteration (27 %). Moderate or severe visual impairment, defined as visual acuity 20/50 or poorer was seen in 71 % of patients with SRD. Poorer visual acuity was correlated with increased central subfield thickness in patients with SRD (r2=0.41, p<0.001). Conclusion SRD were present in 15 % of the uveitis patients reviewed. Moderate to severe vision impairment was present in the majority of eyes (71 %) with SRD. Diffuse macular edema and focal cystoid macular edema were the OCT features most commonly associated with SRD. Intermediate and panuveitis were the most common anatomic sites of inflammation. A variety of pathogenic mechanisms, both inflammatory and non-inflammatory, may be involved in SRD in uveitis patients; identification of the precise mechanism is important for appropriate therapy.This work is supported in part by an Unrestricted Grant from Research to Prevent Blindness (Casey Eye Institute, Emory Eye Center), the Stan and Madelle Rosenfeld Family Trust (JTR), the William and Mary Bauman Foundation (JTR), the William C. Kuzell Foundation (JTR), and the Ronald G. Michels Fellowship Foundation (SY)

A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis

Purpose: The purpose of this study is to elicit the role of oral low-dose sirolimus as a corticosteriod-sparing agent for active uveitis. Methods: A retrospective, interventional case series was performed by reviewing the clinical records of all patients treated with oral, low-dose sirolimus (1-4 mg daily) for severe uveitis. Data reviewed included symptomatic improvement, Snellen best-corrected visual acuity, corticosteroid requirement, sirolimus levels, intraocular inflammation, spectral-domain optical coherence tomography, and fluorescein angiogram. Primary outcome measures were determined by the ability to decrease the intraocular inflammation, corticosteroid requirement, and frequency of flares. Results: Eight patients with varied diagnoses were treated with oral low-dose sirolimus for severe, chronic uveitis between 2008 and 2010. In four of the eight patients, there was an improvement of all primary outcome measures. While sirolimus monotherapy was successful in only one patient, a sirolimus/methotrexate combination was successful in three patients. Although there was a good initial response in three patients, treatment was a failure after serious side effects forced the cessation of sirolimus therapy. One patient was lost to follow-up. Conclusion: Sirolimus may have a limited role in severe uveitis as an adjunct corticosteroid-sparing agent in combination with more standard immunosuppressive agents. Oral low-dose sirolimus appeared to be better tolerated than higher doses, but there were a significant number of adverse events, requiring therapy to be stopped. © 2010 The Author(s)

Optimizing OCT acquisition parameters for assessments of vitreous haze for application in uveitis

Detection and evaluation of inflammatory activity in uveitis is essential to the management of the condition, and yet continues to be largely dependent on subjective clinical measures. Optical coherence tomography (OCT) measurement of vitreous activity is an alternative to clinical vitreous haze scoring and has passed a number of early validation studies. In this study we aimed to evaluate the impact of ‘operator factors’ on the variability of the technique as part of the validation process, and to help evaluate its suitability for ‘real world’ use. Vitreous haze index was calculated as a ratio between the reflectivity of the vitreous and of the outer retina in each scan. Different scanning conditions were tested and their effect on the measurement is reported. Our results show that the ‘quantitative imaging’ technique of OCT-measured vitreous activity had good reliability in normal subjects under a range of ‘real world’ conditions, such as when the operator changes the averaging value. The technique was however vulnerable to highly inaccurate focussing or abnormal downward displacement of the image. OCT-based quantification of vitreous activity is a promising alternative to current subjective clinical estimates, with sufficient ‘tolerance’ to be used in routine clinical practice as well as clinical trials