Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

OBJECTIVES: To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. METHODS: In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. RESULTS: Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. CONCLUSIONS: A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. CLINICAL RELEVANCE STATEMENT: Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. KEY POINTS: • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma.

TOWARD AN IMAGING-CENTRIC DEFINITION OF NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

PURPOSE: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria. METHODS: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease. RESULTS: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone. CONCLUSION: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

High-Risk Histopathological Features of Retinoblastoma following Primary Enucleation: A Global Study of 1426 Patients from 5 Continents.

PURPOSE: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents. METHODS: Retrospective study of 1426 primarily enucleated RB eyes from five continents. RESULTS: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. CONCLUSION: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

MRI Features for Identifying MYCN-amplified RB1 Wild-type Retinoblastoma.

Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes.

PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

Complications of retinopathy of prematurity treatment.

PURPOSE OF REVIEW: The purpose of this review is to summarize complications of treatment for retinopathy of prematurity (ROP) and to compare complications of laser and intravitreal antivascular endothelial growth factor (VEGF) injections. RECENT FINDINGS: Poor structural outcomes and myopia are more common with laser for severe ROP than with anti-VEGF. Clinical trial data show unfavourable outcomes in 9.1-9.5% of laser treated, and 1.4-3.6% of anti-VEGF treated eyes. Additional randomized trial data show risk for very high myopia (≥-8.00D) to be 3.8 and 51.4% for zone I eyes treated with bevacizumab and laser, respectively. However, anti-VEGF may be complicated by late recurrence and is more likely to require retreatment than laser. Laser often necessitates general anaesthesia with its attendant risks, including worse short-term respiratory outcomes. Neurodevelopmental complications have been reported with anti-VEGF, but existing studies are subject to bias. SUMMARY: Treatment complications are substantially different for the two modalities in common use today. In more severe cases, risk of poor structural outcome and myopia favour treatment with anti-VEGF. In less severe ROP, risk of recurrence and the need for additional treatments may favour laser. Additional data are needed to establish comparative risks of neurodevelopmental complications.

Dopamine metabolite levels in the vitreous of diabetic and non-diabetic humans.

Animal studies suggest that the retinal dysfunction in diabetic subjects that precedes overt clinical vasculopathy may be due to a retinal dopamine deficit. We analyzed levels of dopamine (DA) and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the vitreous of diabetic and non-diabetic human subjects. Adult patients undergoing pars plana vitrectomy for non-hemorrhagic indications were prospectively recruited from the Emory Eye Center in Atlanta, GA. Vitreous samples were analyzed using high performance liquid chromatography (HPLC) to measure levels of DOPAC and DA in the vitreous specimens. Vitreous samples from 9 diabetic patients and 20 from non-diabetic patients were analyzed. No eyes had apparent diabetic retinopathy. Mean normalized DA concentration in vitreous of diabetic subjects was 0.76 ± 0.12 pg/µL vs. 0.73 ± 0.08 pg/µL in non-diabetic vitreous (p = 0.849). DOPAC concentration was 8.84 ± 0.74 pg/µL in vitreous of diabetic subjects vs. 9.22 ± 0.56 pg/µL in vitreous of non-diabetic subjects (p = 0.691). No difference was observed in the concentrations of DA and DOPAC in the vitreous of people without diabetes compared to those with diabetes without retinopathy.

EFFECT OF LUBRICANTS ON CORNEAL THICKNESS AFTER VITRECTOMY.

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 µm vs. 58.1 µm, 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.

Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.

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.

Rhegmatogenous Retinal Detachment in Children: Clinical Factors Predictive of Successful Surgical Repair.

PURPOSE: To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective interventional case series. PARTICIPANTS: Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. METHODS: Patients were divided into 3 age groups (0-6 years, 7-12 years, and 13-18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. MAIN OUTCOME MEASURES: Complete reattachment of the retina at final follow-up. RESULTS: Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22-0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2-4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5-8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12-0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1-4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1-5.1) compared with PPV alone (51%). CONCLUSIONS: Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV.

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments.

PURPOSE: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: A total of 61 premature infants with type 1 ROP. METHODS: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. MAIN OUTCOME MEASURES: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. RESULTS: Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. CONCLUSIONS: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration.

PURPOSE: Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression. DESIGN: Retrospective analysis in a prospective study. PARTICIPANTS: Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study. METHODS: Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye. MAIN OUTCOME MEASURES: Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. RESULTS: Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001-0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002-0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008-0.05). CONCLUSIONS: Optical coherence tomography-reflective drusen substructures are optical coherence tomography-based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography-reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

577-NM YELLOW LASER PHOTOCOAGULATION FOR COATS DISEASE.

PURPOSE: To describe the outcomes of children with Coats disease treated with 577-nm yellow laser indirect ophthalmoscopy. METHODS: A retrospective consecutive case series of pediatric patients with Coats disease treated at a single institution between 2011 and 2014. Laser indirect ophthalmoscopy was performed under anesthesia. Full treatment was defined as complete ablation of all visible telangiectasias and resolution of subretinal fluid. No patients were treated with cryotherapy or bevacizumab. RESULTS: Seventeen eyes of 16 patients were consecutively treated. At the time of diagnosis, the eye was classified as Stage 1 (telangiectasias only) in 1 case, Stage 2A (extra-foveal exudation) in 2 cases, Stage 2B (fovea-involving exudation) in 6 cases, Stage 3A1 (extra-foveal exudative retinal detachment) in 2 cases, Stage 3A2 (subtotal foveal-involving detachment) in 1 case, and Stage 3B (total exudative retinal detachment) in 5 cases. The mean age at initial treatment was 71.2 months. Mean length of follow-up was 20.8 months (median 18.5 months, range 3.7-37.3 months). Patients underwent an average of 2.5 laser treatments. Sixteen of 17 eyes achieved full treatment (94.1%) with a mean time-to-full-treatment of 11.2 months. One eye developed glaucoma and end-stage disease. CONCLUSION: 577-nm yellow wavelength laser indirect ophthalmoscopy is an effective treatment for Coats disease including cases of exudative retinal detachment.

Outcomes after Intravitreal Bevacizumab versus Laser Photocoagulation for Retinopathy of Prematurity: A 5-Year Retrospective Analysis.

PURPOSE: To determine the relative effectiveness, major complications, and refractive errors associated with intravitreal bevacizumab (IVB) versus panretinal photocoagulation (PRP) to treat type 1 retinopathy of prematurity (ROP). DESIGN: Retrospective case series. PARTICIPANTS: Consecutive infants with type 1 ROP who received either IVB or PRP and had at least 6 months of follow-up. METHODS: The data from infants treated with either IVB or PRP for type 1 ROP between 2008 and 2012 were recorded from 2 medical centers in Atlanta, Georgia. MAIN OUTCOME MEASURES: Recurrence rate, complication rate, and refractive error. RESULTS: A total of 54 eyes (28 patients) with type 1 ROP were evaluated: 22 eyes (11 patients) received IVB, and 32 eyes (17 patients) received PRP. Among the 22 eyes treated with IVB, 16 eyes had zone I ROP and 6 eyes had posterior zone II ROP. The number of zone I and II ROP eyes treated with PRP were 5 and 27, respectively. Mean gestational age, birth weight, postmenstrual age at initial treatment, and follow-up period for the infants receiving IVB were 24.2 weeks, 668.1 g, 35.1 weeks, and 21.7 weeks, respectively, and for the infants receiving PRP, these were 24.8 weeks, 701.4 g, 36.1 weeks, and 34.5 weeks, respectively. Retinopathy of prematurity recurred in 3 (14%) of 22 IVB-treated eyes and in 1 (3%) of 32 PRP-treated eyes. Neither retinal detachment nor macular ectopia developed in any of the IVB-treated eyes. In PRP-treated eyes, retinal detachment developed in only 1 eye and macular ectopia developed in 5 eyes. Mean spherical equivalent and postgestational age at the last refraction for IVB-treated eyes were -2.4 diopters (D) and 22.4 months, respectively, and for PRP-treated eyes, these were -5.3 D and 37.1 months, respectively. Mean spherical equivalent for zone I ROP eyes treated with IVB and PRP were -3.7 D and -10.1 D, respectively, and for zone II ROP eyes, these were 0.6 D and -4.7 D, respectively. CONCLUSIONS: Both IVB and PRP are effective treatment options for type 1 ROP with low complication rates. IVB was associated with less myopia than PRP, although longer follow-up was available for PRP.

INCIDENCE OF SUSTAINED OCULAR HYPERTENSION USING PREPACKAGED VERSUS FRESHLY PREPARED INTRAVITREAL BEVACIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare the incidence of sustained ocular hypertension (OHT) after intravitreal injections of prepackaged versus freshly prepared bevacizumab monotherapy for the treatment of neovascular age-related macular degeneration. METHODS: Charts of 1,216 patients with neovascular age-related macular degeneration receiving intravitreal bevacizumab monotherapy at 2 retina practices using different preparations of bevacizumab between January 1, 2009, and December 31, 2011, were reviewed. Primary outcome was incidence of sustained OHT, defined as intraocular pressure > 25 mmHg with an increase ≥ 6 from baseline on ≥ 2 consecutive visits or requiring treatment. RESULTS: A total of 6,479 injections in 740 eyes of 634 patients were included and 14 eyes (0.81% incidence per eye-year) developed sustained OHT. For eyes receiving prepackaged bevacizumab, 10 of 339 eyes (1.39% incidence per eye-year) developed sustained OHT compared with 4 of 401 eyes (0.39% incidence per eye-year) receiving freshly prepared bevacizumab, giving an incidence rate ratio of 3.55 (95% confidence interval, 0.93-13.49; P = 0.063). All eyes that developed sustained OHT achieved intraocular pressure control with observation or topical therapy alone. CONCLUSION: Incidence of sustained OHT after intravitreal bevacizumab is low. We found a trend toward higher rates of sustained OHT with prepackaged bevacizumab although this difference was not statistically or clinically significant.

Uveal metastasis from lung cancer: clinical features, treatment, and outcome in 194 patients.

PURPOSE: To evaluate the clinical features, treatment, and prognosis of patients with uveal metastasis from lung cancer. DESIGN: Retrospective chart review. PARTICIPANTS: There were 194 patients with a diagnosis of uveal metastasis from lung cancer. INTERVENTION: Radiotherapy, chemotherapy, enucleation, or observation. MAIN OUTCOME MEASURES: Ocular tumor control, final visual acuity, and tumor-related death. RESULTS: There were 374 uveal metastatic tumors originating from primary lung cancer in 229 eyes of 194 patients. Tumor location included choroid (88%), ciliary body (2%), and iris (10%), with bilateral involvement in 18%. Diagnosis of uveal metastasis preceded the diagnosis of primary lung cancer in 44% of patients. The choroidal metastatic focus had a mean basal diameter of 8 mm and mean thickness of 3 mm, and were mostly located posterior to the equator (91%). The choroidal metastasis commonly had yellow or orange color (98%), had plateau (61%) or dome (38%) configuration, and displayed associated subretinal fluid (85%). Choroidal tumors were multifocal in 49 cases (23%). Ciliary body tumors were commonly dome shaped (75%) with an episcleral sentinel vessel (75%). Iris tumors were multifocal in 2 cases (13%), had visible intrinsic vessels (97%), and were associated with tumor seeding in the angle (38%) or on the iris stroma (25%). The uveal metastases were treated with teletherapy (31%), chemotherapy (18%), brachytherapy (9%), chemotherapy combined with teletherapy or brachytherapy (14%), enucleation (3%), or observation (21%). At last visit, eyes with follow-up showed tumor regression (66%), stability (12%), growth (14%), recurrence (3%), or new metastasis (5%). Visual acuity improved or remained stable in 59% eyes. One-year mortality from the time of detection of uveal metastasis was 54%. CONCLUSIONS: Of 194 patients with uveal metastasis from lung cancer, 44% did not have a history of known lung cancer. Current methods of ocular treatment allow globe salvage in 92% of patients and improved/stable vision in 59% of patients. Systemic prognosis remains poor with tumor-related death in 54% of patients at 1 year.

Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis after intravitreal injection.

PURPOSE: To determine whether the application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce rates of endophthalmitis after intravitreal (IVT) injection. METHODS: We performed in vitro experiments to determine the antibacterial properties of 2% lidocaine/0.1% methylparaben (lidocaine) against causative organisms of endophthalmitis. Isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans from patients with endophthalmitis were incubated with or without lidocaine. Aliquots (100 µL) were plated on Mueller-Hinton (S. aureus and S. epidermidis) or blood agar plates (S. viridans) at 0, 10, 30, 120, and 240 minutes, and colonies were counted after 24 hours. A retrospective review of 15,042 IVT injections was performed from January 2004 to February 2011 to determine the rate of endophthalmitis with or without application of subconjunctival lidocaine for anesthesia. RESULTS: Lidocaine demonstrated rapid bactericidal effects against all 3 organisms. After 10 minutes of exposure, there was approximately a 90% (P < 0.01), 95% (P < 0.001), and 92% (P < 0.001) reduction in colony forming units when compared with time 0 for S. aureus, S. epidermidis, and S. viridans, respectively. Complete elimination of colony forming units occurred at subsequent time points for each organism in contrast to logarithmic increase for control plates. There were a total of 0 cases of endophthalmitis of 6,853 IVT injections performed with subconjunctival lidocaine and 8 cases of endophthalmitis of 8,189 (0.1%) IVT injections performed with other methods of anesthesia (P = 0.03). CONCLUSION: Application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce the incidence of endophthalmitis after IVT injection.

Retinoblastoma with MYCN Amplification Diagnosed from Cell-Free DNA in the Aqueous Humor.

Introduction: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling. Methods: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data. Results: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression. Conclusions: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation. Importance: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.

IODINE-125 PLAQUE BRACHYTHERAPY FOR DIFFUSE CHOROIDAL HEMANGIOMA.

PURPOSE: To report 6 cases of diffuse choroidal hemangioma in children treated with iodine-125 plaque brachytherapy at a single tertiary care center. METHODS: Retrospective case series. RESULTS: Six pediatric patients diagnosed with diffuse choroidal hemangioma were included in the study. Preplaque visual acuity ranged from 20/150 to no light perception. All patients had extensive serous retinal detachment at presentation. An iodine-125 radioactive plaque was placed on the affected eye to administer a dose of 34.2-42.1 Gy to the tumor apex over a median of 4 days. Tumor regression and subretinal fluid resolution were observed in all eyes within 17 months of treatment. Visual acuity improved in two patients. Radiation-induced cataract and subretinal fibrosis were documented in one case, and one patient developed radiation retinopathy. No patients developed neovascular glaucoma within the follow-up time of 12-65 months. CONCLUSION: Iodine-125 plaque radiotherapy is an effective option for diffuse choroidal hemangioma, although there is a risk for radiation-induced complications.