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.

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

Purpose: Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays. Design: Case series study. Participants: Sixty-two RB eyes from 55 children and 14 control eyes from 12 children from 4 medical centers. Methods: This study included 128 RB AH samples including: diagnostic (DX) samples, samples from eyes undergoing treatment (TX), samples after completing treatment (END), and during bevacizumab injection for radiation therapy after completing RB treatment (BEV). Fourteen-control AH were analyzed for unprocessed analytes (double-stranded DNA [dsDNA], single-stranded DNA [ssDNA], micro-RNA [miRNA], RNA, and protein) with Qubit fluorescence assays. Double-stranded DNA from 2 RB AH samples underwent low-pass whole-genome sequencing to detect somatic copy number alterations. Logistic regression was used to predict disease burden given analyte concentrations. Main Outcome Measures: Unprocessed analyte (dsDNA, ssDNA, miRNA, RNA and protein) concentrations. Results: Results revealed dsDNA, ssDNA, miRNA, and proteins, but not RNA, were quantifiable in most samples (up to 98%) with Qubit fluorescence assays. Median dsDNA concentration was significantly higher in DX (3.08 ng/μl) compared to TX (0.18 ng/μl; P < 0.0001) at an order of 17 times greater and 20 times greater than END samples (0.15 ng/μl; P = 0.001). Using logistic regression, nucleic acid concentrations were useful in predicting higher versus lower RB disease burden. Retinoblastoma somatic copy number alterations were identified in a TX, but not in a BEV sample, indicating the correlation with RB activity. Conclusions: Aqueous humor liquid biopsy in RB is a high-yield source of dsDNA, ssDNA, miRNA, and protein. Diagnostic samples are most useful for RB 1 gene mutational analyses. Genomic analysis may be more informative of tumor activity status than quantification alone and can be performed even with smaller analyte concentrations obtained from TX samples. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Purpose: This study examines the impact of corneal surface lubricants used during pars plana vitrectomy on corneal edema. Methods: This prospective, observational, clinical study occurred at an academic institution. Participants were individuals aged 18 years and older who had already consented to undergo pars plana vitrectomy, without pre-existing corneal pathology. A corneal lubricant was chosen by the surgeon. Corneal thickness was measured preoperatively and postoperatively using pachymetry and anterior segment optical coherence tomography (AS-OCT). Main outcome measure was change in corneal thickness as measured by pachymetry. Results: Forty-one patients completed the study protocol. The 23 subjects in the SHCS group had a significantly smaller increase in corneal thickness as measured by pachymetry compared with the 18 subjects in the HPMC group (29.9 mm vs. 58.1 mm, P value 0.02). When measured by anterior segment optical coherence tomography, the SHCS group had a smaller increase in corneal thickness compared with the HPMC group (0.04 mm vs. 0.06 mm, P value 0.09) but did not reach significance. Conclusion: SHCS is associated with reduced postoperative increase in corneal pachymetry as compared to HPMC.

Purpose: To report results of aflibercept therapy in eyes with neovascular age-related macular degeneration previously treated with bevacizumab, ranibizumab, or both. Design: Retrospective, interventional, noncomparative, consecutive case series. Methods: Ninety-six eyes from 85 patients with neovascular age-related macular degeneration who previously had received bevacizumab, ranibizumab, or both were treated with aflibercept monthly for 3 months followed by a fourth injection within 2 months. Outcomes were determined 4 ± 1 months after the first aflibercept dose and included: proportion of patients gaining or losing 2 lines or more of best-corrected visual acuity, proportion remaining within a gain or loss of 1 line, mean change in logarithm of the minimal angle of resolution visual acuity, mean change in central foveal thickness, mean change in macular cube volume, and qualitative anatomic response as assessed by spectral-domain optical coherence tomography. Results: At baseline, 82 (85%) eyes had signs of active exudation despite a mean of 17 previous anti-vascular endothelial growth factor injections. At final visit, 82 (85%) remained stable within a gain or loss of 1 line, 7 (7%) gained 2 lines or more, and 7 (7%) lost 2 lines or more of best-corrected visual acuity. Mean logarithm of the minimal angle of resolution visual acuity showed minimal change 0.02 (range, -0.46 to 0.70; P =.14). Mean central foveal thickness decreased -18 μm (range, -242 to 198 μm; P =.06). Mean macular volume decreased -0.27 mm3 (95% confidence interval, -0.4 to -0.1 mm3; P =.004). On qualitative analysis, 4 (5%) eyes had complete resolution of exudative fluid, 40 (49%) showed partial resolution, 26 (32%) remained unchanged, and 12 (14%) showed worsened exudative fluid. Conclusions: Aflibercept seems to be an effective alternative for neovascular age-related macular degeneration patients previously treated with bevacizumab, ranibizumab, or both at 4 months of follow-up. Most treated eyes demonstrated stable visual acuity and anatomic improvements by spectral-domain optical coherence tomography.

Purpose: To review the clinical features, treatment outcomes, and prevalence within our clinic population of adolescents and adults with previously regressed retinopathy of prematurity (ROP) who demonstrate late-onset exudation and vasoproliferative changes. Design: Retrospective review of consecutive patients at a single center. Participants: Five patients (5 eyes) with a history of ROP who showed new exudates or worsening fibrovascular proliferation diagnosed after 10 years of age. Methods: Patients were identified by a computerized search of the Emory Eye Center billing records. Data extracted from charts included baseline ROP information, visual acuity and other examination findings, imaging, and treatments. Main Outcome Measures: Status of exudation and vasoproliferation. Results: Among 138 patients older than 10 years with ROP seen at our tertiary referral center from 2000 through 2018, 5 (3.6%) demonstrated late-onset exudation or vasoproliferation. Three patients were female and 3 underwent ROP treatment as neonates. Mean age at onset of late reactivation was 25.6 years (range, 13–43 years). Previous treatments for neonatal ROP included peripheral laser ablation (n = 3), scleral buckle (n = 2), pars plicata vitrectomy (n = 2), and no treatment (n = 2). Management strategies for late reactivation included observation (n = 1), intravitreal anti–vascular endothelial growth factor agents (n = 4), vitrectomy (n = 2), and cryotherapy (n = 1). With mean follow-up of 4.8 years (range, 1–7 years), outcomes were resolution of exudation or proliferation with return to baseline vision (n = 2), stable mild exudation (n = 1), and progressive vasoproliferation with traction leading to phthisis (n = 2). Conclusions: Late-onset exudation and fibrovascular proliferation in adolescents and adults with ROP can occur rarely with previously regressed ROP. Two of 5 patients were refractory to all treatments and demonstrated phthisis bulbi. One patient showed reactivation in the form of a reactive retinal astrocytic tumor. Our findings highlight the importance continued monitoring with regular fundus examination in adolescents and adults with regressed ROP.

A 4-week-old boy with subependymal lesions consistent with tuberous sclerosis was evaluated for a large intraocular tumor in the left eye. The eye was enuclated and examination showed a retinal giant cell astrocytoma composed of giant, round cells and spindle-shaped cells, with associated aggregates of mononuclear inflammatory cells.

Purpose of review The surgical management of ROP continues to employ a paradigm of peripheral laser followed by vitrectomy for patients who develop retinal detachment. This review addresses significant advances that have been made in our understanding of the indications, timing, techniques, and outcomes of these interventions. Recent findings The indications for laser are highly dependent upon the diagnosis of plus disease. Recognition of plus disease is variable and subjective. Efforts are underway to develop more objective measures of plus using image analysis software. Intravitreal injection of bevacizumab is emerging as an adjunct to laser for aggressive posterior ROP. While vitrectomy for retinal detachment is effective in eyes without plus, management of eyes with retinal detachment and persistent plus continues to be a major challenge. Older children with regressed ROP may suffer from vitreous hemorrhage in the absence of retinal tears, detachments, or active neovascularization. Summary Our understanding of the best indications, timing and techniques for the surgical management of ROP continues to evolve and outcomes have improved in recent years. Areas that generate significant ongoing interest and investigation include the assessment of plus disease and the use of adjuncts for aggressive posterior ROP.

Purpose The purpose of this study was to characterize the peripheral retinal findings in highly myopic young children without other known risk factors for retinal detachment. Methods A retrospective review of all cases of children ≤10 years of age with high myopia (>6.00 diopters) who were evaluated for presumed risk of retinal detachment by either an examination under anesthesia or office examination by a single retina specialist from January 2001 through December 2008. Patients with regressed retinopathy of pre-maturity, retinal detachment in the fellow eye, or known Stickler syndrome were excluded. Results Fifty-four eyes of 30 patients with high myopia were examined. Twenty-six eyes of 14 patients were examined under anesthesia because of the examiner’s inability to adequately visualize the peripheral retina during an office examination. Mean age at examination was 6 ± 3 (range, 1–10) years. Mean spherical equivalent refractive error was −13.88 ± 3.79 (range, −6.00 to −25.00) diopters. Peripheral retinal findings were identified in 33% of eyes, the most common being lattice degeneration (20%), white without pressure (11%), and retinal holes with subretinal fluid (4%). Conclusion Approximately one third of highly myopic children in our study showed peripheral retinal findings. If the peripheral retina is not adequately visualized during an office evaluation, examination under anesthesia should be considered.

Purpose: Determine the efficacy of combination intravitreal and systemic antiviral therapy for the treatment of acute retinal necrosis (ARN) and risk factors impacting visual acuity (VA) and retinal detachment (RD) outcomes. Design: Single-center retrospective case series. Participants: Patients with an ARN diagnosis based on clinical features and polymerase chain reaction confirmation who were treated at a tertiary referral, university-based academic practice. Methods: Patient records were reviewed for demographic information including age and gender. Snellen VA, disease findings including RD outcomes, optic nerve involvement, and treatments were recorded. Incidence rates of major VA and RD outcomes were calculated based on the number of events and exposure times. Cox proportional hazards regression modeling and survival analyses were used to identify factors related to VA and RD outcomes over time. Main Outcome Measures: Logarithm of the minimal angle of resolution VA, 2-line or more VA gain, severe vision loss (SVL) of 20/200 or worse, RD development, and fellow eye involvement. Results: Twenty-three eyes of 21 patients (11 male, 10 female) were reviewed. Thirteen patients (62%) had herpes simplex virus and 8 patients (38%) had varicella zoster virus. The event rate for 2-line or more VA gain was 0.49 events/eye-year (95% confidence interval [CI], 0.26–0.86 events/eye-year), whereas the rate of SVL was 0.61 events/eye-year (95% CI, 0.34–1.02 events/eye-year). Retinal detachment development was observed at a rate of 0.59 events/eye-year (95% CI, 0.33–1.00 events/eye-year). Thirteen of 23 eyes (57%) demonstrated RD with a mean time of 120 days after ARN diagnosis. With each additional quadrant of retina involved, a greater risk of RD development over time was observed (hazard ratio, 2.21; 95% CI, 1.12–4.35). Nine percent of eyes progressed with additional quadrantic involvement, despite combination systemic and intravitreal antiviral therapy; however, none of the 19 patients demonstrating unilateral ARN showed fellow-eye involvement after initiation of therapy. Conclusions: Combination intravitreal and systemic antiviral therapy for ARN can be effective in improving VA and limiting retinitis progression. Each additional quadrant of retina involved was associated with a 2.2-fold greater risk of RD, which may impact monitoring, timing of intervention, and patient counseling.