Pediatric glaucoma suspects: characteristics and outcomes.

PURPOSE: To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma. METHODS: This was a retrospective sequential cohort study of children <18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma. RESULTS: A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar. CONCLUSIONS: Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP >24 and presence of a periocular lesion carry higher risk.

Simultaneous Versus Sequential Ptosis and Strabismus Surgery in Children.

PURPOSE: The authors sought to compare the clinical outcomes of simultaneous versus sequential ptosis and strabismus surgery in children. METHODS: Retrospective, single-center cohort study of children requiring both ptosis and strabismus surgery on the same eye. Simultaneous surgeries were performed during a single anesthetic event; sequential surgeries were performed at least 7 weeks apart. Outcomes were ptosis surgery success (margin reflex distance 1 ≥ 2 mm, good eyelid contour, and good eyelid crease); strabismus surgery success (ocular alignment within 10 prism diopters of orthophoria and/or improved head position); surgical complications; and reoperations. RESULTS: Fifty-six children were studied, 38 had simultaneous surgery and 18 sequential. Strabismus surgery was performed first in 38/38 simultaneous and 6/18 sequential cases. Mean age at first surgery was 64 months, with mean follow up 27 months. A total of 75% of children had congenital ptosis; 64% had comitant strabismus. A majority of ptosis surgeries were frontalis sling (59%) or Fasanella-Servat (30%) procedures. There were no significant differences between simultaneous and sequential groups with regards to surgical success rates, complications, or reoperations (all p > 0.28). CONCLUSIONS: In the first comparative study of simultaneous versus sequential ptosis and strabismus surgery, no advantage for sequential surgery was seen. Despite a theoretical risk of postoperative eyelid malposition or complications when surgeries were performed in a combined manner, the rate of such outcomes was not increased with simultaneous surgeries. Performing ptosis and strabismus surgery together appears to be clinically effective and safe, and reduces anesthesia exposure during childhood.

Timely implementation of a retinopathy of prematurity telemedicine system.

PURPOSE: To examine the feasibility of a retinopathy of prematurity (ROP) telemedicine evaluation system of providing timely feedback to a neonatal intensive care unit (NICU) with at-risk premature infants. METHODS: This was a prospective observational study of premature infants with birth weights of <1251 g in five NICUs in the United States. Infants scheduled for clinically indicated ROP evaluations underwent indirect ophthalmoscopic examinations and digital imaging on the same day. Imaging was performed by nonphysician retinal imagers. Times required were determined from obtaining digital images of both eyes to submission via web-based system to a secure server for grading by trained readers at a central reading center to sending back grading results to the clinical center. RESULTS: A total of 1,642 image sets of eyes of 292 infants were obtained, from 823 imaging sessions. The mean turnaround time from submission of image sets of both eyes to return of the grading results to the clinical center was 10.1 ± 11.3 hours (standard deviation), with a median of 12.0 hours (1st quartile, 0.9 hours; 3rd quartile, 16 hours). Overall, 95.5% of gradings (95% CI, 93.9%-96.7%) were returned within 24 hours. Subgroup analyses found, for image sets submitted to the reading center before 2 p.m. Eastern Standard Time, median time to report was 1.7 hours (1st quartile, 0.7 hours; 3rd quartile, 15.5 hours) compared with those submitted after 2pm (median, 14.1 hours; 1st quartile, 11.2, hours; 3rd quartile, 16.3 hours). CONCLUSIONS: An ROP telemedicine approach can provide timely feedback to the NICU regarding the detection of potentially serious ROP and thus referral to an ophthalmologist for examination and consideration of treatment.

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.

Uveitis Reactivation in Children Treated With Tumor Necrosis Factor Alpha Inhibitors.

PURPOSE: To evaluate reactivation of pediatric uveitis during/following treatment with tumor necrosis factor alpha inhibition (anti-TNFα). DESIGN: Retrospective cohort study. METHODS: We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed. RESULTS: Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be "at risk" of the primary (19 for the secondary) outcome. 60% were female, ∼half had juvenile idiopathic arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9%-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9%-87.7%]) vs before (21.6% [95% CI: 10.8%-40.2%]) anti-TNFα discontinuation. Among those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs infliximab (hazard ratio [HR] 13.4, P = .01, 95% CI: 2.2-82.5) and those with older age at uveitis onset (HR 1.3, P = .09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years. CONCLUSIONS: Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at 1 year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression for more than 1.5 years decreases the reactivation risk.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

PURPOSE: To describe the retinal structure in a patient with cobalamin C (cblC) disease. METHODS: A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). RESULTS: The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. CONCLUSIONS: A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

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.

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.

The rate of change in retinal vessel width and tortuosity in eyes at risk for retinopathy of prematurity.

PURPOSE: To describe the rate of change in retinal vessel width and tortuosity in eyes that develop treatment-requiring, or type 1, retinopathy of prematurity (ROP) versus eyes that do not develop type 1 ROP. METHODS: Posterior poles of eyes of 41 infants at risk for ROP were imaged longitudinally with a 30° fundus camera. Retinal vessel width and tortuosity were measured with computer-assisted image analysis. The rate of change per day in width and tortuosity up to the development of most severe ROP was calculated from linear regression and eyes with (n = 10) and without type 1 ROP (n = 31) were compared. RESULTS: Eyes that developed type 1 ROP had a greater rate of change in width for venules and 3 widest vessels (P < 0.0001), and a greater rate of change in tortuosity for arterioles and 3 most tortuous vessels (P < 0.0001) than eyes that did not develop type 1 ROP. These vessel parameters discriminate the 2 groups well (area under the ROC curve, 0.79-0.90). A combination of venular width and arteriolar tortuosity had the best discriminative ability (area under the ROC curve, 0.96). CONCLUSIONS: In this pilot study, eyes that eventually developed type 1 ROP demonstrated a faster increase in width and tortuosity of retinal vessels compared with those that did not. Further study of the kinetics of retinal vascular change in a larger sample may allow for the earlier identification of vision-threatening ROP.

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 Children's 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.

Retinal vessel changes after laser treatment for retinopathy of prematurity.

BACKGROUND: The clinical response to retinopathy of prematurity (ROP) treatment is currently assessed subjectively. This study aims to quantify treatment response objectively by assessing changes in digital images of posterior pole retinal vessel width and tortuosity. METHODS: Images of 30 right eyes with type 1 ROP obtained at up to three time points were analyzed: before treatment (T = 0) and 1 (T = 1) and/or 2 weeks (T = 2) after treatment. Width and tortuosity of retinal vessels were analyzed from digital images using computer-assisted image analysis software. RESULTS: Vessel width decreased by 20% (P < 0.004) within the first week and remained stable by the second week after laser treatment. Vessel tortuosity did not significantly change by the first week but decreased 27% (P < 0.01) by second week. CONCLUSIONS: Vessel width appears to decrease dramatic within the first week, whereas the regression of tortuosity follows a slower course.

Comparison of expert graders to computer-assisted image analysis of the retina in retinopathy of prematurity.

AIMS: To determine correlation of width and tortuosity between expert graders and computer-assisted image analysis of the retina in narrow-field images of eyes with retinopathy of prematurity. METHODS: 11 digital images were selected based on severity of retinopathy of prematurity (ROP). Narrow field images were analysed for width and tortuosity of vessels using computer-aided image analysis of the retina (CAIAR), an image analysis software, and by four ROP experts. Spearman correlation coefficients (ρ) assessed the correlation of CAIAR grading with expert grading. Intra-class correlations assessed agreement among graders. Width and tortuosity were compared among severity of ROP and treatment status using analysis of variance and generalised estimating equations. RESULTS: Expert measurements correlated well with measures from CAIAR for venule width (ρ=0.57-0.66) and arteriole tortuosity (ρ=0.71-0.81). Measurements from four graders agreed moderately well (intra-class correlations were 0.49 and 0.69 for venule width and arteriole tortuosity, respectively). Increased severity of ROP (no pre-plus/plus, pre-plus, plus) was associated with larger width (linear trend p=0.02 in two graders) and tortuosity (linear trend p<0.03 in all graders). Tortuosity measurements by CAIAR and graders were statistically different between treated and untreated eyes (p<0.002). CONCLUSIONS: We found moderate correlation between expert graders' assessment of vessel tortuosity and width and CAIAR using narrow-field images.

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.

Simultaneous bilateral intraocular surgery in children.

BACKGROUND: Simultaneous bilateral intraocular surgery (SBIS), defined as sequential bilateral intraocular surgery completed in one visit to the operating room, is a controversial topic. The reluctance of ophthalmologists to perform SBIS has been mainly attributable to concerns about bilateral catastrophic complications (endophthalmitis, expulsive hemorrhage, or retinal detachment). Herein we report our experience with SBIS in children and review the literature. METHODS: The medical records of 44 patients who underwent 48 cases of SBIS between 1994 and 2009 were reviewed. Of the 48 cases, 27 were bilateral cataract extractions, 1 including intraocular lens placement; 21 were cases of bilateral glaucoma surgeries, including goniotomy, trabeculotomy, and filtering tube placement. Bilateral surgeries were performed in one session under general anesthesia with strict aseptic separation of the 2 surgeries. RESULTS: All but one of the cataract cases were performed in patients <1 year of age, and the majority (15/27) were performed in patients < or =1 month of age. Postoperative complications included aphakic glaucoma (5 patients) and reproliferation of lens material (3 patients). The majority of patients who underwent glaucoma procedures were <1 year of age (19/21), with 4 of 21 <1 month of age. One eye developed hyphema that required anterior chamber wash out. There were no catastrophic complications from the surgery or anesthesia (death, asphyxia, cardiac or respiratory arrest, or seizures) in either group. CONCLUSIONS: Simultaneous bilateral intraocular surgery was performed safely in 48 cases during a 15-year period. In selected pediatric cases requiring bilateral intraocular surgery for glaucoma or cataract, SBIS may reduce risks related to anesthesia and delayed surgery.

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.

Image analysis of posterior pole vessels identifies type 1 retinopathy of prematurity.

Identification of type 1 retinopathy of prematurity (ROP) relies heavily on the presence of characteristics of plus disease, especially tortuosity. However, a relatively infrequent subset of eyes with type 1 ROP, eyes with zone 1, stage 3 ROP without plus disease, is included in treatment indications. We examined if posterior pole vessel width is associated with type 1 ROP in a subset of eyes with zone 1, stage 3 ROP without plus disease and whether vessel width differentiates type 1 from non-type 1 ROP.

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.

Computerized analysis of retinal vessel width and tortuosity in premature infants.

PURPOSE: To determine, with novel software, the feasibility of measuring the tortuosity and width of retinal veins and arteries from digital retinal images of infants at risk of retinopathy of prematurity (ROP). METHODS: The Computer-Aided Image Analysis of the Retina (CAIAR) program was developed to enable semiautomatic detection of retinal vasculature and measurement of vessel tortuosity and width from digital images. CAIAR was tested for accuracy and reproducibility of tortuosity and width measurements by using computer-generated vessel-like lines of known frequency, amplitude, and width. CAIAR was then tested by using clinical digital retinal images for correlation of vessel tortuosity and width readings compared with expert ophthalmologist grading. RESULTS: When applied to 16 computer-generated sinusoidal vessels, the tortuosity measured by CAIAR correlated very well with the known values. Width measures also increased as expected. When the CAIAR readings were compared with five expert ophthalmologists' grading of 75 vessels on 10 retinal images, moderate correlation was found in 10 of the 14 tortuosity output calculations (Spearman rho = 0.618-0.673). Width was less well correlated (rho = 0.415). CONCLUSIONS: The measures of tortuosity and width in CAIAR were validated using sequential model vessel analysis. On comparison of CAIAR output with assessments made by expert ophthalmologists, CAIAR correlates moderately with tortuosity grades, but less well with width grades. CAIAR offers the opportunity to develop an automated image analysis system for detecting the vascular changes at the posterior pole, which are becoming increasingly important in diagnosing treatable ROP.