Ocular and developmental outcomes of a dosing study of bevacizumab for retinopathy of prematurity.

PURPOSE: To report 2-year ocular and developmental outcomes for infants receiving low doses of intravitreal bevacizumab for type 1 retinopathy of prematurity (ROP). METHODS: A total of 120 premature infants (mean birthweight, 687 g; mean gestational age, 24.8 weeks) with type 1 ROP were enrolled in a multicenter, phase 1 dose de-escalation study. One eye per infant received 0.25 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreal bevacizumab; fellow eyes when treated received one dosage level higher. At 2 years, 70 of 120 children (58%) underwent ocular examinations; 51 (43%) were assessed using the Bayley Scale of Infant and Toddler Development. RESULTS: Correlation coefficients for the association of total dosage of bevacizumab with Bayley subscales were -0.20 for cognitive (95% CI, -0.45 to 0.08), -0.15 for motor (95% CI, -0.41 to 0.14), and -0.19 for language (95% CI, -0.44 to 0.10). Fourteen children (21%) had myopia greater than -5.00 D in one or both eyes, 7 (10%) had optic nerve atrophy and/or cupping, 20 (29%) had strabismus, 8 (11%) had manifest nystagmus, and 9 (13%) had amblyopia. CONCLUSIONS: In this study cohort, there was no statistically significant correlation between dosage of bevacizumab and Bayley scores at 2 years. However, the sample size was small and the retention rate relatively low, limiting our conclusions. Rates of high myopia and ocular abnormalities do not differ from those reported after larger bevacizumab doses.

Intraoperative Mounted Optical Coherence Tomography Findings Following Reversal of Optic Nerve Head Cupping in Childhood Glaucoma.

PURPOSE: To examine the structural changes occurring in the optic nerve head (ONH) and macula in infants with childhood glaucoma and clinically observed ONH cupping reversal following intraocular pressure (IOP)-reducing glaucoma surgery, as captured by intra-operative spectral-domain optical coherence tomography (SD-OCT). DESIGN: Retrospective observational case series from an ongoing prospective cohort study. METHODS: Included were 18 eyes of 14 patients with childhood glaucoma. All eyes had SD-OCT imaging pre- and post-glaucoma intervention and clinically identified ONH cupping reversal. Patients with poor quality images or persistent optic nerve swelling following IOP reduction were excluded. Outcome measurements included IOP, cup-to-disc ratio, axial length and SD-OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), transverse horizontal diameter of Bruch membrane opening (BMO-D), cup depth, and macula. RESULTS: Mean age at surgery was 1.14±0.93 years and mean interval between pre- and post-operative imaging was 127 days (range 35-595). Following intervention, mean IOP reduction was 45%, accompanied by significant reductions in the cup-to-disc ratio (0.30±0.12, p<0.001), axial length (0.43±0.28mm, p<0.001) and cup depth (46%, p<0.001). Mean global pRNFL thickness pre- vs. post-treatment was 93.1±14.7µm vs. 93.1±17.1µm, respectively, p=1.0. There was no significant difference in pre- and post-treatment global or sectoral pRNFL, 3mm macular total and segmented retinal layer volumes, or the BMO-D. CONCLUSIONS: Clinical ONH cupping reversal after IOP-lowering surgery was associated with axial length reduction and decrease in cup depth, but no significant change in the pRNFL or macular volume measures. ONH cupping reversal likely marks stabilization but any pre-intervention ONH damage persists.

The shrinking eye: dimensional changes in the young child's eye after glaucoma drainage device implantation for refractory childhood glaucoma.

PURPOSE: To investigate the magnitude of reduction in the axial length (AL) and corneal diameter following glaucoma drainage device (GDD) placement and intraocular pressure (IOP) reduction in glaucoma patients <3 years of age at surgery. METHOD: The medical records of consecutive childhood glaucoma patients who underwent GDD implantation at a single practice between 2013 and 2018 and were <3 years of age at surgery were reviewed retrospectively. Demographics, glaucoma diagnoses, surgical details, and pre- and post-procedure measurements of AL, IOP, corneal diameter, central corneal thickness, presence of corneal edema, and cup:disk ratio were analyzed. RESULTS: A total of 16 eyes of 10 patients were included. Before GDD placement, mean AL was 23.49 ± 3.05 mm. Mean AL reduction after placement was 0.80 ± 0.85 mm (P = 0.001); median AL reduction, 0.93 mm (range, -3.05 to +0.59). Mean IOP reduction after GDD placement was 15.0 ± 6.0 mm Hg (P < 0.0001). IOP reduction and AL reduction were significantly related (P = 0.0013). Mean corneal diameter before GDD placement was 13.0 ± 1.6 mm; mean corneal diameter reduction after placement was 0.3 ± 0.3 mm (P = 0.012). Reduction of corneal diameter and of AL were significantly related (P = 0.03); corneal diameter and IOP were not (P = 0.40). Objective cupping reversal after GDD was noted in 50% of eyes with documented cup:disk ratio. CONCLUSIONS: In this study cohort, reduction in AL, corneal diameter, and cup:disk ratio was found to be correlated with reduced IOP after GDD placement. This result merits consideration during surgical planning for glaucoma patients <3 years of age.

Longitudinal reproducibility of spectral domain optical coherence tomography in children with physiologic cupping and stable glaucoma.

PURPOSE: To determine whether Spectralis (Heidelberg, Germany) spectral domain optical coherence tomography (SD-OCT) measurements are reproducible over time in children with physiologic cupping and stable glaucoma. METHODS: Subjects were identified from a subset of participants in an earlier retrospective study conducted by our group and included children (<18 years of age) with physiologic cupping and stable primary congenital glaucoma (PCG) having had at least 2 SD-OCTs over a period of more than 1 between April 2010 and September 2015. Thicknesses of average peripapillary retinal nerve fiber layer (pRNFL) and six individual sectors and volumes of three segmented retinal layers and total retina were measured. Spectralis review software was used for segmentation. Intraclass correlation coefficients (ICC) and coefficient of variation (COV) were calculated. RESULTS: A total of 35 eyes of 35 children were included: 15 eyes had physiologic cupping; 20 eyes, PCG. Mean ages at initial SD-OCT were 11.2 ± 3.3 years and 9.7 ± 3.3, respectively; mean intervals between first and last imaging were 2.2 ± 1.1 and 3.0 ± 1.4 years, respectively. ICCs across three visits for both groups for average and sectoral pRNFL thicknesses were 0.887-0.997 and for segmented retinal volumes were 0.806-0.993. ICCs for total retinal volume for physiologic cupping and PCG were 0.993 and 0.954, respectively. COVs for average pRNFL thickness were 0.9% and 1.7%, respectively. For all other measurements, COVs ranged from 0.3% to 5.4%. CONCLUSIONS: Reproducibility of longitudinal SD-OCT measurements for average pRNFL thickness in children with stable glaucoma over about 2 years is comparable to short-term reproducibility (COV) in normal children (1.16%) and normal and glaucoma adults (1.62%-3.4%).

The effect of repeated measurements and the use of topical anesthetic on rebound tonometry values in children.

Measurement of intraocular pressure (IOP) in children is important in the management of pediatric glaucoma. Availability of the Icare rebound tonometer has greatly facilitated our ability to obtain awake IOP in infants and children, but little has been reported on either the effect of repeated sequential IOP measurements with Icare or the effect of topical anesthetic on subsequent Icare tonometry. This prospective study of 20 eyes of 10 cooperative children (12 normal eyes, 8 with suspected or known glaucoma) found that neither 8 sequential Icare measurements nor application of topical anesthetic produced a statistically or clinically signficant change in measured IOP by rebound tonometry.

Cupping reversal in pediatric glaucoma--evaluation of the retinal nerve fiber layer and visual field.

PURPOSE: To identify optic nerve head (ONH) cupping reversal and associated optical coherence tomography (OCT) and Humphrey visual field changes in pediatric glaucoma. DESIGN: Retrospective observational case series. METHODS: Sequential surgical cases of juvenile open-angle glaucoma (OAG) or primary congenital glaucoma (PCG) with sustained postoperative intraocular pressure (IOP) reduction. Group 1 had preoperative and postoperative ONH photographs and OCT; Group 2 had preoperative clinical ONH assessment and postoperative imaging. Cupping evaluation was confirmed by masked glaucoma and neuro-ophthalmology specialists. RESULTS: Of 80 cases, 9 eyes (9 children) met criteria for Group 1; 24 eyes (19 children) met criteria for Group 2. Group 1: Five of 9 eyes (56%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 34.2 ± 6.6 mm Hg vs 10.6 ± 4.1 mm Hg (P < .00001) and mean average retinal nerve fiber layer (RNFL) 71.0 ± 30 µm vs 62.8 ± 24 µm (P = .4), respectively. RNFL was stable in 4 of 5 eyes (all juvenile OAG), but thinned (Δ = -41 µm) in 1 eye with PCG. Humphrey visual fields (reliable in 2 of 3 eyes) showed no significant change. Group 2: Fourteen of 24 PCG eyes (58%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 36.1 ± 8.9 mm Hg vs 13.3 ± 2.1 mm Hg (P < .00001). Two eyes had thin RNFL postoperatively despite healthy-appearing ONH. Postoperative RNFL showed statistically significant linear correlation with preoperative (but not postoperative) cup-to-disc ratio. Limitations include small numbers, few reliable Humphrey visual fields, and absent preoperative imaging (Group 2). CONCLUSION: Some eyes with IOP reduction and ONH cupping reversal show continued RNFL thinning postoperatively. The preoperative ONH cup-to-disc ratio predicted the postoperative RNFL better than the postoperative "reversed and smaller" cup-to-disc ratio. Cupping reversal in pediatric glaucoma may not predict improved ONH health and deserves further study.

Optical coherence tomography in paediatric glaucoma: time domain versus spectral domain.

BACKGROUND/AIMS: Spectral-domain (SD)- Optical Coherence Tomography (OCT) can track eye movements, has faster acquisition time and higher resolution than time-domain(TD)-OCT. The aim of the study was to assess the utility of SD-OCT in paediatric glaucoma and determine its agreement with TD-OCT. METHODS: Children who had SD-OCT(Spectralis, Heidelberg-Engineering,Germany) were retrospectively and prospectively identified from Duke paediatric glaucoma clinic. The peripapillary retinal nerve fibre layer (RNFL) and macular thickness and volume (MV) were compared amongst four groups: normal eyes, eyes with physiologic cupping (C:D >0.5 and <0.8, IOP <21), mild glaucomatous eyes (C:D <0.5, intra-ocular pressure (IOP) >21) and severe glaucoma (C:D>0.5, IOP>21). SD-OCT values were compared to TD-OCT(OCT-3, Carl-Zeiss-Meditec, Dublin, CA) values in a subset of subjects who had same day scans using both instruments. Children with neurologic disorders, refractive error >±5D, pseudophakia and prematurity were excluded. RESULTS: Included were 83 eyes of 83 children, mean age 11.9 ± 4.2 years. SD-OCT measurements of average RNFL thickness and MV differed among normals(n=24), physiologically cupped (n=31), mild (n=15) versus severe glaucoma (n=13): (RNFL:104 ± 9, 99 ± 6, 98 ± 9 vs 62 ± 18 µm, respectively, p<0.05; MV: 8.7 ± 0.3, 8.6 ± 0.3, 8.8 ± 0.4 vs 8.0 ± 0.6 mm³;, respectively, p<0.05). Same-day SD-OCT and TD-OCT measures in 53 eyes correlated linearly (RNFL r(2)=0.88; MVr(2)=0.58). SD-OCT measured lower RNFL and higher macular thickness than TD-OCT. Among eyes with severe glaucoma, 4 of 13 (30%) had unreliable TD-OCT but reliable SD-OCT. CONCLUSIONS: SD-OCT was easier to obtain than TD-OCT in children. SD-OCT and TD-OCT measurements correlated, but values were not interchangeable.

Longitudinal reproducibility of optical coherence tomography measurements in children.

PURPOSE: To evaluate the longitudinal reproducibility of optical coherence tomography (OCT) measurements in normal and glaucomatous eyes of children. METHODS: In this 2-setting prospective study, OCT-3 was used to obtain fast retinal nerve fiber layer (RNFL) and macular thickness scans. In the first study setting, the normal eyes of healthy children were scanned on presentation, at 2 weeks, and 3 years, with axial length measured at the first and last examinations. In the second setting, OCT scans of patients in the pediatric glaucoma clinic were performed over 4 years as clinically indicated. Eyes were classified as "normal" (normal eyes and those with physiologic cupping but normal intraocular pressure [IOP]); "mild glaucoma" (increased IOP and a normal optic nerve appearance); or "advanced glaucoma" (severe cupping or progressive glaucoma). Intraclass correlation coefficients were used to evaluate the reproducibility of measurements on the same day and over time. RESULTS: In the first setting, 8 normal eyes were included. Axial length increased 0.11 ± 0.04 mm/year over an average of 3.3 years (P = 0.03); there was no statistically significant change in RNFL thickness (P = 0.30). In our second setting, 27 normal eyes and 37 eyes with glaucoma were included. Intraclass correlation coefficients across the 3 visits for total macular volume were 0.80-0.91 and for average RNFL were 0.73-0.95. CONCLUSIONS: Global OCT measurements in children were reproducible over years and were not affected by normal increase in axial length. OCT shows promise as an objective tool for longitudinal assessment of children.

Differentiating glaucomatous from non-glaucomatous optic nerve cupping by optical coherence tomography.

BACKGROUND: In clinical practice, the differentiation of glaucomatous from non-glaucomatous cupping can be difficult, even for experienced observers. The purpose of this study was to evaluate the role of optical coherence tomography (OCT) in differentiating glaucomatous from non-glaucomatous optic nerve cupping in a cross-sectional pilot study. METHODS: Eleven consecutive patients presenting to the Duke Eye Center from September 2007 to July 2008 with non-glaucomatous optic nerve cupping and 12 patients with glaucomatous optic nerve cupping were identified. All patients underwent Stratus® OCT imaging: fast macular map, fast retinal nerve fiber layer (RNFL) 3.4 thickness, and fast optic disc protocols. Automated visual field perimetry was performed on the date of OCT scan in non-glaucomatous cupping patients, and from 0-9 months of scan date in glaucoma patients. Eyes were matched by optic nerve cup-to-disc area ratio; average and mean deviation were calculated for each variable. RESULTS: For a similar average RNFL, patients with non-glaucomatous optic nerve cupping had lower nasal and temporal RNFL thickness, as well as lower macular thickness and volume compared to patients with glaucomatous optic nerve cupping. CONCLUSION: OCT appears to be a useful technology in differentiating glaucomatous from non-glaucomatous optic nerve cupping. The pattern of RNFL loss appears more diffuse in non-glaucomatous optic nerve cupping compared to glaucomatous optic nerve cupping. Future studies with larger sample size and specific neuro-ophthalmic causes of optic nerve cupping may further elucidate the role of OCT in this clinical setting.