Association of Health Insurance Status With Severity and Treatment Among Infants With Retinopathy of Prematurity.

This study describes retinopathy of prematurity treatment practices using Medicaid and commercial claims databases. Infants with Medicaid tend to be sicker overall and have higher rates of retinopathy of prematurity requiring treatment than those with commercial insurance. Among patients who required treatment, those with Medicaid were more likely to receive anti-vascular endothelial growth factor than laser treatment. [J Pediatr Ophthalmol Strabismus. 2023;60(6):e75-e78.].

Exudative retinal detachment after laser in retinopathy of prematurity.

Treatment of retinopathy of prematurity with laser photocoagulation can be very effective in preventing future blindness, but its complications should be well understood by the ophthalmologists performing the treatment. We present the case of a 4-month-old girl in whom laser photocoagulation led to an exudative retinal detachment in both eyes. The fluid eventually resolved after treatment with topical and systemic steroids, but the effects of persistent fluid led to permanent photoreceptor loss. Optical coherence tomography can be useful in diagnosing the complication of exudative retinal detachment after laser photocoagulation and monitoring treatment response.

Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).

Smartphone application links severity of retinopathy of prematurity to early motor behavior in a cohort of high-risk preterm infants.

PURPOSE: To evaluate the General Movement Assessment (GMA) with the Motor Optimality Score-Revised (MOS-R) as a neurodevelopmental marker in infants with retinopathy of prematurity (ROP). METHODS: Infants screened prospectively for ROP were evaluated at 3 months' post-term age using a smartphone application to complete the GMA and MOS-R. Results were analyzed by ROP severity. RESULTS: Of 105 enrolled infants, 83 completed the study. Of these, 54 (65%) had any ROP, 32 (39%) had severe ROP, and 13 (16%) had type 1 ROP. The proportion with aberrant GMA was significantly higher in infants with severe ROP (14/32 [44%]) compared with infants who had milder ROP (8/51 [16%]; P = 0.006). Of those with severe ROP, there was no significant difference comparing infants with type 1 ROP treated with bevacizumab (7/13 [54%]) to infants with type 2 ROP without treatment (7/19 [37%]; P = 0.47). Although the presence of any ROP, stage of ROP, and severe ROP each predicted lower MOS-R scores on univariate analyses, only severe bronchopulmonary dysplasia and markers of brain injury remained significant in the multivariate analysis. CONCLUSIONS: The GMA was a convenient, short-term method of data collection with low attrition. Although severe ROP initially appeared linked to poor early motor scores, this association is likely confounded by neurological and respiratory complications, which frequently accompany severe ROP.

Late Vitreoretinal Complications of Regressed Retinopathy of Prematurity: Retinal Break, Vitreous Hemorrhage, and Retinal Detachment.

PURPOSE: To investigate late vitreoretinal complications and visual outcomes in patients with regressed retinopathy of prematurity (ROP) with or without prior treatment. DESIGN: International, multicenter, noncomparative retrospective case series. PARTICIPANTS: We analyzed 264 eyes of 238 patients from 13 centers worldwide who developed vitreoretinal complications (retinal detachment [RD], vitreous hemorrhage [VH], or retinal break) ≥ 2 years after resolution of acute ROP. METHODS: Each participant was assigned to 1 of 3 groups (the RD, VH, and retinal break groups) according to their primary diagnosis. The average age at presentation, visual acuities, refractive error, axial length, gestational age, birth weight, acute ROP classification, prior treatments for acute ROP, postoperative visual acuity (VA), and concomitant eye conditions in the 3 groups were documented and compared. MAIN OUTCOME MEASURES: Clinical features and visual outcomes of late vitreoretinal complications in patients with regressed ROP. RESULTS: A total of 264 eyes of 238 patients were included. The prior acute ROP status was comparable among the 3 groups, except that the VH group had a higher proportion of patients with type 1 ROP (P = 0.03) and prior treatment (P < 0.001) than the other groups. The average age at presentation was earlier in the RD (20.3 ± 15.5 years) and VH (21.4 ± 18.9 years) groups than in the retinal break group (31.9 ± 18.2 years; P < 0.001). The retinal break group had the best presenting best-corrected VA, followed by the RD and VH groups (P < 0.001). Surgical intervention improved VA in both the RD and VH groups (both P < 0.05). The overall trend of VA was the most favorable in the retinal break group, followed by that in the VH and RD groups. Cicatricial changes in the fellow retina were observed in > 90% of patients with unilateral involvement. CONCLUSIONS: Infants with acute ROP remain at a high risk of vision-threatening complications throughout childhood and adulthood. Continual follow-up of patients with ROP is important. When severe complications, such as RD or VH, are detected, timely surgical intervention is necessary to ensure favorable visual outcomes in these patients.

Single shot quantitative polarized light imaging system for rapid planar biaxial testing of soft tissues.

Quantitative Polarized Light Imaging (QPLI) is an established technique used to compute the orientation of collagen fibers based on their birefringence. QPLI systems typically require rotating linear polarizers to obtain sufficient data to estimate orientation, which limits acquisition speeds and is not ideal for its application to mechanical testing. In this paper, we present a QPLI system designed with no moving parts; a single shot technique which is ideal to characterize collagen fiber orientation and kinematics during mechanical testing. Our single shot QPLI system (ssQPLI) sorts polarized light into four linear polarization states that are collected simultaneously by four cameras. The ssQPLI system was validated using samples with known orientation and retardation, and we demonstrate its use with planar biaxial testing of mouse skin. The ssQPLI system was accurate with a mean orientation error of 1.35° ± 1.58°. Skin samples were tested with multiple loading protocols and in each case the mean orientation of the collagen network reoriented to align in the direction of primary loading as expected. In summary, the ssQPLI system is effective at quantifying collagen fiber organization, and, when combined with mechanical testing, can rapidly provide pixel-wise measures of fiber orientation during biaxial loading.

The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti.

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

Exudative Retinal Detachment Following Chimeric Antigen Receptor T-Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia.

Chimeric antigen receptor (CAR) T-cell therapy has become a novel approach in the treatment of many hematologic malignancies. However, ocular adverse effects have not been well described. This report presents a case of a pediatric patient with relapsed B-cell acute lymphoblastic leukemia with ocular involvement treated with CAR T-cell therapy who developed an exudative retinal detachment likely secondary to an inflammatory response to CAR T-cell therapy. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:113-115.].

Laser Prophylaxis in Patients with Stickler Syndrome.

PURPOSE: To evaluate the association among laser prophylaxis treatment, retinal detachment (RD), and visual acuity (VA) in patients with Stickler syndrome (SS). DESIGN: Retrospective comparative case series. PARTICIPANTS: Patients with SS. METHODS: Patients received extended vitreous base laser (EVBL), nonprotocol laser (NPL), or no laser prophylaxis treatment of any kind. MAIN OUTCOME MEASURES: The 2 main outcome measures that were examined in these patients were rates of RD and VA. RESULTS: In this study, 230 eyes of 115 patients were included. Fifty-nine patients were women (51%). The median age at the time of laser prophylaxis treatment was 9.5 years (interquartile range [IQR], 6-13 years), and the median age of patients with RD was 11 years (IQR, 7-18 years). Of the 230 eyes, 92 did not undergo any laser treatment, 9 received NPL treatment, and 129 received EVBL treatment. Of the 129 eyes that underwent EVBL treatment, 4 (3%) had RD, compared with 74 eyes (73%) that had RD and did not receive laser or NPL treatment (P < 0.001). Eyes that received EVBL treatment had approximately 8 lines better vision, on average, compared with those that did not receive laser or NPL treatment (-0.86 logarithm of the minimum angle of resolution; 95% confidence interval,-1.1 to -0.64; P < 0.001). CONCLUSIONS: Treatment with EVBL seems to reduce the rate of subsequent RD and is associated with better VA in patients with SS.

Retinoblastoma presenting as pseudohypopyon and preserved visual acuity.

PURPOSE: To describe a Case of retinoblastoma that presented subtly as a pseudohypopyon in a child with preserved visual acuity. OBSERVATIONS: A 3-year-old male was referred for concern of hypopyon in the left eye. Initial examination revealed 20/30 vision, a pseudohypopyon, and a large white mass on fundoscopy. Examination under anesthesia revealed extensive retinoblastoma with vitreous seeds and anterior chamber involvement. Enucleation was performed and histology demonstrated retinoblastoma with tumor cells found within the ciliary body, iris, iridocorneal angle, and Schlemm canal. Based on the high-risk histopathology findings, adjuvant chemotherapy was performed. CONCLUSIONS AND IMPORTANCE: Retinoblastoma is the most common primary intraocular malignancy in children. Though the classic presentation is leukocoria and/or strabismus, it can present in a variety of ways. Physicians should be aware that retinoblastoma, even severe forms, can present subtly with pseudohypopyon and preserved vision. Adjuvant chemotherapy for anterior segment involvement remains controversial.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study.

PURPOSE: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB). DESIGN: International, multicenter, retrospective, interventional case series. PARTICIPANTS: Patients with SIB from 23 centers with RRD in at least 1 eye. METHODS: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed. MAIN OUTCOME MEASURES: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity. RESULTS: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9%) and trisomy 21 (21.8%) and the most common behavior was face hitting (74.4%). The average follow-up time was 3.3 ± 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3%), primary scleral buckle (SB; 26.9%), and vitrectomy with SB (39.7%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5%) with RRDs were inoperable. The SSAS was 23.1% without tamponade (37.2% if including silicone oil), and final reattachment was attained in 80% (36.3% without silicone oil tamponade). Funnel-configured RRD (P = 0.006) and the presence of grade C proliferative vitreoretinopathy (P = 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P = 0.008. These associations held if restricting to 64 patients with ≥12 months followup. Anatomic reattachment correlated with better visual acuity (P < 0.001). CONCLUSIONS: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.

Macular Sequelae Following Exudative Retinal Detachment After Laser Photocoagulation for Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE: To report a series of exudative retinal detachments (ERDs) following laser photocoagulation for retinopathy of prematurity (ROP). PATIENTS AND METHODS: Retrospective case series. RESULTS: Eleven eyes of seven infants were identified who developed ERD following laser. Median gestation age was 25 weeks (interquartile range [IQR]: 24-27 weeks), and median birth weight was 662 grams (IQR: 538-850 grams). Median postmenstrual age at time of laser was 35 weeks (IQR: 33-39 weeks). ERD was diagnosed at a median of 7 days (IQR: 5-7 days) after laser and was managed with steroids. Bevacizumab was also used for certain cases. Time to resolution ranged from 1 to 5 weeks. Macular pigment changes, atrophy, window defect on fluorescein angiography, and photoreceptor loss on optical coherence tomography were noted in some cases following ERD resolution. Excluding one patient who expired at 3 months, median length of follow-up was 10 years (IQR: 9-13.5 years). Overall, only one patient, who presented with less severe ERD, had normal vision. CONCLUSIONS: ERD is an uncommonly reported complication following laser for ROP. Macular changes following ERD resolution may have negative visual consequences. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:698-705.].

Two-Year Outcomes Comparing Anti-VEGF Injections to Laser for ROP Using a Commercial Claims Database.

BACKGROUND AND OBJECTIVE: To report ocular and neurodevelopmental outcomes among infants treated for retinopathy of prematurity (ROP) in a nationwide health insurance claims database. PATIENTS AND METHODS: Retrospective cohort study of 298 infants treated with laser or anti-vascular endothelial growth factor (VEGF) injection identified in the MarketScan database (2011-2017) with 2-year follow-up. RESULTS: A review of claims data found 298 patients with International Classification of Diseases and Common Procedural Technology codes for ROP treatment and 2 years of continuous insurance coverage. Of these, 63 infants received injections and 235 received laser. Overall, the anti-VEGF group had higher rates of underlying neurological comorbidities (35% vs. 23%; P = .05) and thrombocytopenia (17% vs. 8%; P = .02). Most ocular outcomes were similar, including retinal detachment (P = .87). There were higher rates of second procedures after injection (44% vs. 10%; P < .001). Rates of language, motor, and cognitive delays were similar. Rates of cerebral palsy were higher with injections but were not statistically significant after adjusting for comorbidities (odds ratio = 1.88; P = .10). CONCLUSIONS: The prevalence of retinal detachment after 2 years was similar comparing anti-VEGF to laser. Despite the higher rates of underlying neurologic comorbidity in the injection group, there were no differences in language, motor, or cognitive delays. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:486-493.].

Late visual outcomes in infants treated with primary bevacizumab for type 1 retinopathy of prematurity.

PURPOSE: To describe visual acuity findings after 4 years of age in infants treated with primary bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) and to correlate structural findings on fluorescein angiography (FA) with functional outcomes. METHODS: Infants born between January 2011 and January 2014 were identified by review of the medical records. Visual acuity was measured in clinic after 4 years of age. As described in the ET-ROP study, normal visual acuity was 20/40 (logMAR 0.3) or better. Examination under anesthesia with FA and prophylactic laser if necessary was recommended for all patients who received primary IVB. Vascular abnormalities were reviewed by 2 experts. RESULTS: A total of 23 infants (46 eyes) completed visual acuity testing. Median age was 6 years (IQR, 4-7). Median visual acuity was logMAR 0.18 (IQR, 0-0.3). Normal vision was recorded for 39/46 (85%) eyes. Twenty-one patients (42 eyes) completed an examination under anesthesia with FA. All eyes had some peripheral capillary abnormalities (shunts, tangles, or abnormal branching); most had peripheral nonperfusion (90%) and leakage (64%). CONCLUSIONS: Most eyes treated with IVB for type 1 ROP had normal visual acuity. Our results after IVB in this study compare favorably to 6-year visual outcomes in the ET-ROP study, in which 34.6% of early-treated eyes had normal visual acuity (20/40 or better). Nonetheless, a high percentage of eyes had abnormal vascular patterns on FA, which may be related to underlying ROP or to treatment. Peripheral vascular changes are common in eyes with ROP treated with IVB, but they do not preclude excellent visual acuity.

Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity.

PURPOSE: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy. DESIGN: Retrospective, nonconsecutive, noncomparative, multicenter case series. PARTICIPANTS: Three hundred sixty-three eyes of 186 patients. METHODS: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings. MAIN OUTCOME MEASURES: Rate of RDs and factors conferring a higher risk of RDs. RESULTS: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009). CONCLUSIONS: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.