Monte D. Mills

Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite

Background: Visual dysfunction is one of the most common causes of disability in multiple sclerosis (MS). The Multiple Sclerosis Functional Composite (MSFC), a new clinical trial outcome measure, does not currently include a test of visual function. Objective: To examine contrast letter acuity as a candidate visual function test for the MSFC. Methods: Binocular contrast letter acuity testing (Sloan charts) was performed in a subgroup of participants from the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial (IMPACT Substudy) and in MS patients and disease-free control subjects from a cross-sectional study of visual outcome measures (Multiple Sclerosis Vision Prospective cohort [MVP cohort]). High-contrast visual acuity was measured in both studies; MVP cohort participants underwent additional binocular testing for contrast sensitivity (Pelli–Robson chart), color vision (D-15 desaturated test), and visual field (Esterman test, Humphrey Field Analyzer II). Results: Contrast letter acuity (Sloan charts, p < 0.0001, receiver operating characteristic curve analysis) and contrast sensitivity (Pelli–Robson chart, p = 0.003) best distinguished MS patients from disease-free control subjects in the MVP cohort. Correlations of Sloan chart scores with MSFC and Expanded Disability Statue Scale (EDSS) scores in both studies were significant and moderate in magnitude, demonstrating that Sloan chart scores reflect visual and neurologic dysfunction not entirely captured by the EDSS or MSFC. Conclusions: Among clinical measures, contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli–Robson chart) demonstrate the greatest capacity to identify binocular visual dysfunction in MS. Sloan chart testing also captures unique aspects of neurologic dysfunction not captured by current EDSS or MSFC components, making it a strong candidate visual function test for the MSFC.

Glaucoma following childhood cataract surgery.

Glaucoma has been recognized as an infrequent but serious complication following surgery for congenital and acquired cataracts in childhood. Little is known concerning the influence of factors on the risk of glaucoma such as age at surgery, type of cataract, associated ocular abnormalities, and type of surgery. We reviewed records of 240 eyes of 155 patients on whom cataract surgery had been performed between January 1965 and July 1990 at Childrens Hospital, Boston. After excluding those patients who had been followed up less than 5 years after surgery, and those who had had surgery after the age of 10 years, 125 eyes of 82 patients were included in the study group. We identified 14 eyes of 9 patients that had developed open-angle glaucoma 5.3 to 13.1 years following surgery (average 7.4 years). An additional 4 eyes of 3 patients developed angle closure glaucoma, which was diagnosed at 146, 177, 2911, and 2939 days following surgery. A fifth patient developed acute angle closure 1.7 years following primary cataract surgery and 53 days following secondary discission. All but one of the patients who developed glaucoma had cataract surgery at less than 1 year of age. Age at surgery for the entire study group averaged 1.9 years, and ranged from 25 days to 9.6 years. We conclude that patients having cataract surgery before 1 year of age are at the greatest risk of developing postoperative open-angle glaucoma. Additional increased relative risk was found in eyes with microcornea, congenital rubella syndrome, and poor pupillary dilation with 1% cyclopentolate (Cyclogyl). No significant difference was seen among the various surgical methods of cataract removal.

Telemedicine screening for retinopathy of prematurity in developing countries using digital retinal images: a feasibility project.

PURPOSE To determine the feasibility in a middle-level human development country of onsite training, image collection, Internet transfer, and remote grading of digital retinal images from babies screened for retinopathy of prematurity (ROP). METHODS Two experienced nurses in a neonatal nursery in Lima, Peru, were trained to take posterior pole (30 degrees ) digital retinal images. Nurses obtained posterior pole retinal images from babies undergoing routine ROP screening and selected images for uploading via Internet for remote evaluation by five masked ROP experts. Results of gradings were compared with same-day clinical diagnostic examinations by an experienced ophthalmologist. Success rates for image acquisition and transfer for grading by expert readers were calculated. RESULTS Serial image sets from 26 of the 28 babies enrolled in this study were obtained; two babies were too unstable for imaging. Fifty-six of 58 (96.6%) imaging sessions were successful in obtaining retinal images. Three hundred thirty of 336 (98.2%) images obtained were successfully uploaded to an interactive database. Remote graders judged 93.6% to 97.3% of image sets suitable for ROP grading. Preliminary results indicate sensitivities for detection of serious ROP from 45.5% to 95.2% among individual readers, with specificities of 61.7% to 96.2% when images were gradable. CONCLUSIONS A telemedicine approach for ROP screening using digital retinal images obtained by nonophthalmologists is feasible in rapidly developing countries that lack ROP-trained ophthalmologists. If remote grading of digital images is validated as an effective method for identifying referral-warranted ROP (RW-ROP), images obtained by nonphysicians may provide a means of identifying babies who require a diagnostic examination by an ophthalmologist.

Response of pediatric uveitis to tumor necrosis factor-α inhibitors.

Objective. To evaluate the outcome of tumor necrosis factor-α inhibition (anti-TNF) for pediatric uveitis. Methods. We retrospectively assessed children (age ≤ 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥ 2 consecutive ophthalmological examinations ≥ 28 days apart while taking no oral and ≤ 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. Results. Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%–87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%–76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%–80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%–31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%–43%). Conclusion. Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF.

Visual acuity outcomes in pediatric glaucomas

PURPOSE To evaluate and compare the visual acuity prognosis in the various pediatric glaucoma subtypes and to determine risk factors for vision loss. METHODS The medical records of pediatric glaucoma patients from 2000 to 2010 at Childrens Hospital of Philadelphia were retrospectively reviewed. Visual acuities, surgeries, glaucoma subtype, and etiology of vision impairment were recorded. Univariate and multivariate analyses were performed to determine the risk factors for visual impairment. RESULTS A total of 133 eyes (36.8% primary congenital glaucoma, 28.6% aphakic glaucoma, 12.0% glaucoma associated with anterior segment dysgenesis, 12.0% Sturge-Weber glaucoma) of 88 patients were included. At last follow-up (median length, 5 years), 46.6% eyes achieved excellent (≥20/70) visual acuity. Of the glaucoma subtypes, primary congenital glaucoma conferred the best visual prognosis, with 69.4% eyes with excellent (≥20/70) visual acuity at final follow-up. Factors most associated with visual impairment (<20/200) were unilateral disease, multiple surgeries, poor vision at diagnosis, and other ocular comorbidities. The most common primary etiology for vision impairment was amblyopia (54.9%). CONCLUSIONS Patients with glaucoma early in life appear to have a better visual acuity prognosis than previously reported, with those with primary congenital glaucoma faring better than other glaucoma subtypes. Recognition of risk factors for visual impairment can better guide clinical management and counseling of patients.

Semiautomated digital image analysis of posterior pole vessels in retinopathy of prematurity

Plus disease is a major indicator for treatment in retinopathy of prematurity (ROP), and computer-assisted image analysis of vessel caliber and tortuosity in the posterior pole may indicate disease progression and severity. We sought to determine whether semiautomated digital analysis of posterior pole vessels using narrow field images with varying severity of ROP correlated with vessel width and tortuosity.

The Rate of Retinal Vessel Dilation in Severe Retinopathy of Prematurity Requiring Treatment

PURPOSE To assess whether the rate of change of retinal vessel diameter can help identify infants at the highest risk for severe retinopathy of prematurity (ROP). DESIGN Thirty-five infants at risk for ROP were included in this prospective, longitudinal study. METHODS Images were obtained using the NIDEK NM200D noncontact camera (NIDEK Inc, Aichi, Japan) at the time of ROP examinations in the intensive care unit. Vessel diameters were measured from digital fundus photographs of right eyes in a masked fashion using VesselMap image analysis software (IM-EDOS GmbH, Weimar, Germany). The rate of change of vessel diameter was calculated based on the linear regression slope and was compared between eyes in which type 1 ROP requiring treatment developed and in controls without ROP or with ROP less severe than type 1. RESULTS Multivariate analysis showed that the group of eyes in which type 1 ROP developed had a greater increase in diameter over time in the inferior temporal veins (P = .01), superior temporal veins (P < .0001), mean temporal veins (P < .0001), superior temporal arteries (P = .02), and mean temporal arteries (P = .004). The area under receiver operator characteristic curve for venous diameter change was 0.96 for the superior temporal vein, 0.86 for the inferior temporal vein, and 0.96 for the mean temporal vein. CONCLUSIONS On average, the rate of retinal vessel change was greater in eyes with type 1 ROP requiring treatment than in control eyes. The rate of venous diameter change had the best discriminative ability to differentiate between the 2 groups.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

PURPOSE To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. METHODS Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. RESULTS Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. CONCLUSIONS Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

Risk Stratification of Preplus Retinopathy of Prematurity by Semiautomated Analysis of Digital Images

OBJECTIVE To determine whether quantitative analysis of retinal vessel width and tortuosity from digital images discriminates which eyes with preplus retinopathy of prematurity (ROP) progress to treatment severity. METHODS Posterior pole images of eyes at first clinical diagnosis of preplus ROP were obtained using a 30 degrees-field, noncontact fundus camera. Width and tortuosity of retinal vessels were analyzed from digital images using computer-assisted image analysis software. Mean width and tortuosity of venules and arterioles were compared in 19 preplus eyes that regressed spontaneously and 11 preplus eyes that progressed to treatment severity. Receiver operating characteristic curve analysis was performed to assess whether width and tortuosity discriminated between groups. RESULTS Mean widths of venules alone, arterioles alone, and the 3 widest vessels were higher in preplus progressed eyes (P < .04). Mean tortuosity of the 3 most tortuous vessels was higher in preplus progressed than in preplus regressed eyes (P = .01). Most vessel width and tortuosity variables predicted which eyes with preplus progressed to treatment moderately well, with an area under the receiver operating characteristic curve of 0.72 to 0.82. CONCLUSIONS Digital image analysis of retinal vessel width and tortuosity may be useful in predicting which preplus ROP eyes will require treatment. Because vascular abnormalities are a continuum and clinical diagnosis is subjective, quantitative analysis may improve risk stratification for ROP.

Interactive Retinal Vessel Extraction by Integrating Vessel Tracing and Graph Search

Despite recent advances, automatic blood vessel extraction from low quality retina images remains difficult. We propose an interactive approach that enables a user to efficiently obtain near perfect vessel segmentation with a few mouse clicks. Given two seed points, the approach seeks an optimal path between them by minimizing a cost function. In contrast to the Live-Vessel approach, the graph in our approach is based on the curve fragments generated with vessel tracing instead of individual pixels. This enables our approach to overcome the shortcut problem in extracting tortuous vessels and the problem of vessel interference in extracting neighboring vessels in minimal-cost path techniques, resulting in less user interaction for extracting thin and tortuous vessels from low contrast images. It also makes the approach much faster.