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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.

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. “Referral warranted” eye disease is present at birth in about 5.5% of term infants, with “macular hemorrhage impinging on the fovea” representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on “referable macular hemorrhage” (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:3–6.]

Purpose The purpose of this report is to describe a patient who has fluorescein angiographic evidence and retinal changes suspicious for intrauterine abusive ocular trauma. Methods A case report of a premature ward of the state with no prenatal care and a presentation suspicious for intrauterine abusive ocular trauma. We performed serial ophthalmologic examinations, reviewed available prenatal history with the infant's social worker, and all relevant hospital notes, laboratory results, and imaging results. Results Following initial empiric treatment for possible viral retinitis in the setting of a positive urine CMV, repeat examinations demonstrated fluorescein angiographic evidence and clinical findings suspicious for abusive ocular trauma including neovascularization and no evidence of retinitis; therefore, the child was treated with laser photocoagulation. Conclusion At-risk newborns will benefit from an examination of the retinal periphery and wide field fluorescein angiography. Intrauterine abusive ocular trauma should be included in the differential of retinal hemorrhage and avascular retinal periphery. It is imperative for clinicians to recognize this presentation to prevent progression of associated visual morbidity.

While Inherited Retinal Diseases (IRDs) are typically considered rare diseases, Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie Disease (ND) are more rare than retinitis pigmentosa. We wanted to determine if multigenic protein-altering variants are common in FEVR subjects within a set of FEVR-related genes. The potential occurrence of protein-altering variants in two different genes has been documented in a very small percentage of patients, but potential multigenic contributions to FEVR remain unclear. Genes involved in these orphan pediatric retinal diseases are not universally included in available IRD targeted-sequencing panels, and cost is also a factor limiting multigenic-sequence-based testing for these rare conditions. To provide an accurate solution at lower cost, we developed a targeted-sequencing protocol that includes seven genes involved in Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie disease. Seventy-six DNA samples from persons refered to clinic with possible FEVR and some close relatives were sequenced using a novel Oakland-ERI orphan pediatric retinal disease panel (version 2) providing 900 times average read coverage. The seven genes involved in FEVR/ND were: NDP (ChrX), CTNNB1 (Chr3); TSPAN12 (Chr7); KIF11 (Chr10), FZD4 (Chr11), LRP5 (Chr11), ZNF408 (Chr11). A total of 33 variants were found that alter protein sequence, with the following relative distribution: LRP5 13/33 (40%), FZD4 9/33 (27%), ZNF408 6/33 (18%), (KIF11 3/33 (9%), NDP 1/33 (3%), CTNNB1 1/33 (3%). Most protein-altering variants, 85%, were found in three genes: FZD4, LRP5, and ZNF408. Four previously known pathogenic variants were detected in five families and two unrelated individuals. Two novel, likely pathogenic variants were detected in one family (FZD4: Cys450ter), and a likely pathogenic frame shift termination variant was detected in one unrelated individual (LRP5: Ala919CysfsTer67). The average number of genes with protein-altering variants was greater in subjects with confirmed FEVR (1.46, n = 30) compared to subjects confirmed unaffected by FEVR (0.95, n = 20), (p = 0.009). Thirty-four percent of persons sequenced had digenic and trigenic protein-altering variants within this set of FEVR genes, which was much greater than expected in the general population (3.6%), as derived from GnomAD data. While the potential contributions to FEVR are not known for most of the variants in a multigenic context, the high multigenic frequency suggests that potential multigenic contributions to FEVR severity warrant future investigation. The targeted-sequencing format developed will support such exploration by reducing the testing cost to $250 (US) for seven genes and facilitating greater access to genetic testing for families with this very rare inherited retinal disease.

To investigate late vitreoretinal complications and visual outcomes in patients with regressed retinopathy of prematurity (ROP) with or without prior treatment.International, multicenter, noncomparative retrospective case series.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.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.Clinical features and visual outcomes of late vitreoretinal complications in patients with regressed ROP.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 (P0.001) 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; P0.001). The retinal break group had the best presenting best-corrected VA, followed by the RD and VH groups (P0.001). Surgical intervention improved VA in both the RD and VH groups (both P0.05). 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 in90% of patients with unilateral involvement.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.

Purpose To describe the spectrum of retinal vascular abnormalities in patients with phakomatosis pigmentovascularis (PPV). Design Multicenter, retrospective, noncomparative, consecutive case series. Methods Eligible patients underwent detailed retinal examination including indirect ophthalmoscopy. Ultra-widefield fundus imaging, including color fundus photography and angiography, was performed using standardized protocols, and findings were recorded and reviewed and analyzed. Participants Three patients with a clinical diagnosis of PPV are presented. Results Evaluation of all patients (n = 6 eyes of 3 patients) with widefield fluorescein angiography showed several retinal vascular abnormalities, including peripheral retinal nonperfusion (n = 3 eyes), peripheral vascular leakage (n = 3 eyes), aberrant retinal vessels (n = 1 eyes), vascular tortuosity (n = 1 eyes), and disruption of the foveal avascular zone including fovea plana (n = 3 eyes). In addition, 2 eyes demonstrated peripheral retinal vascular straightening and leakage similar to the features of familial exudative vitreoretinopathy. One of the patients was a carrier of a somatic GNA11 R183C pathogenic variant that has been associated with PPV. Conclusions Fluorescein angiography, especially with widefield capability, reveals numerous retinal vascular abnormalities in patients with PPV. Considering the association of GNA11 pathogenic variants with PPV and allied disorders, these observations may suggest a role of guanine-binding proteins (G-proteins) in retinal vascular development. Supplemental material available at www.ophthalmologyretina.org.

BACKGROUND AND OBJECTIVE: To quantify vessel tortuosity among infants with retinopathy of prematurity (ROP). PATIENTS AND METHODS: This was a retrospective study including 61 RetCam images from 33 infants. The laser treatment (LT) group included 17 infants who underwent laser for ROP. The no-treatment (NT) group included 16 infants. The modified ROPtool was used to calculate mean vessel tortuosity (MVT) and highest vessel tortuosity (HVT) for the participants and for the standard plus disease photograph from the Early Treatment for Retinopathy of Prematurity (ETROP) study. RESULTS: The median MVT was 1.226 versus 1.056 for the LT and NT groups, respectively ( P < .001). The median HVT was 1.346 versus 1.088 ( P < .001). An MVT of 1.124 was 96.7% sensitive and 100% specific for identifying infants with treatment-requiring ROP. Both MVT and HVT cutoff values correctly captured plus disease in the standard ETROP trial photograph. CONCLUSION: The modified ROPtool can be used to identify infants who have treatment-requiring ROP with a high level of sensitivity and specificity. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:215–220.]

Purpose To evaluate the natural history of congenital X-linked retinoschisis (CXLRS) and to assess disease stability or progression over time. Design Retrospective case series at a single-center, tertiary care, pediatric retina practice. Participants One hundred two eyes of 51 patients with CXLRS. Methods The clinical examinations, fundus photographs, and OCT images of all patients with CXLRS were assessed. Eyes that initially demonstrated combined retinoschisis–retinal detachments and those with large, centrally overhanging schisis cavities were excluded from the analysis (n = 49) because they underwent surgery, which precluded observation of the natural disease course. Main Outcome Measures Stability or conversion of CXLRS phenotype over time. Results Fifty-three eyes met inclusion criteria for observation of natural disease history over time. At the time of diagnosis, 7.5% of eyes showed type 1 disease (n = 4), 17% showed type 2 disease (n = 9), 66% showed type 3 disease (n = 35), and 9.5% showed type 4 disease (n = 5). Mean length of follow-up was 7.4 years. A total of 7.5% of eyes demonstrated a combined retinoschisis–retinal detachment requiring surgery (n = 4), whereas 1.8% demonstrated a large, centrally overhanging schisis cavity requiring surgery (n = 1). Overall, 83% of eyes (n = 44) remained the same type without conversion or development of a complication requiring surgery. The remaining 17% of eyes (n = 9) experienced some type of change from their baseline diagnosis, with 7.5% (n = 4) converting between phenotypes and 9.5% (n = 5) demonstrating a complication requiring surgery; 3.75% of eyes (n = 2) converted from type 2 to 3 and 7.5% of eyes (n = 4) converted from type 3 to a combined retinoschisis–retinal detachment with mean time to conversion of 4.07 years. Conclusions This longitudinal study conveyed the natural history of CXLRS. Congenital X-linked retinoschisis displayed long-term stability in 83% of eyes with conversion or progression of the disease to a more severe phenotype in the remaining cases. Type 3 CXLRS was a risk factor for the development of a combined retinoschisis–retinal detachment and may benefit from closer follow-up.

Purpose To determine the incidence of endophthalmitis after anti–vascular endothelial growth factor (VEGF) therapy at our institution and to identify potential risk factors for endophthalmitis occurring after injection. Design Retrospective, single-center cohort study. Participants All patients who received an intravitreal injection of an anti-VEGF medication between January 1, 2014, and March 31, 2017. Methods Current Procedural Terminology and International Classification of Diseases billing codes were used to identify instances of anti-VEGF administration and cases of endophthalmitis. Medical records and injection technique were reviewed carefully in each case. Multivariable logistic regression analysis was performed in a stepwise fashion to determine independent predictors of endophthalmitis based on injection protocol. Main Outcome Measures Incidence of endophthalmitis after injection and odds of endophthalmitis by injection technique with 95% confidence intervals (CIs). Results A total of 154 198 anti-VEGF injections were performed during the period of interest, resulting in 58 cases of endophthalmitis (0.038% [1:2659]). After adjustment for confounders, both 2% lidocaine jelly (odds ratio [OR], 11.28; 95% CI, 3.39–37.46; P Conclusions The incidence of endophthalmitis after anti-VEGF injections is low. Use of lidocaine jelly or Tetravisc may increase the risk of endophthalmitis after injection.

OBJECTIVE: To evaluate the clinical utility of a quantitative deep-learning derived vascular severity score for retinopathy of prematurity (ROP) by assessing its correlation with clinical ROP diagnosis and by measuring clinician agreement in applying a novel scale. DESIGN: Analysis of existing database of posterior pole fundus images and corresponding ophthalmoscopic examinations using two methods of assigning a quantitative scale to vascular severity. SUBJECTS AND PARTICIPANTS: Images were from clinical exams of patients in the Imaging & Informatics in ROP consortium. 4 ophthalmologists and 1 study coordinator evaluated vascular severity on a 1-9 scale. METHODS: A quantitative vascular severity score (1-9) was applied to each image using a deep learning algorithm. A database of 499 images was developed for assessment of inter-observer agreement. MAIN OUTCOME MEASURES: Distribution of deep learning derived vascular severity scores with the clinical assessment of zone (I,II,III), stage (0,1,2,3) and extent (6 clock hours) of stage 3 evaluated using multivariable linear regression. Weighted kappa and Pearson correlation coefficients for inter-observer agreement on 1-9 vascular severity scale. RESULTS: For deep learning analysis, a total of 6344 clinical examinations were analyzed. A higher deep learning derived vascular severity score was associated with more posterior disease, higher disease stage, and higher extent of stage 3 disease (P

To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections.Multicenter, retrospective series.From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumabbevacizumab; P0.001).Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

Purpose To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis type 2 (MacTel2), using widefield fluorescein angiography (WFA). Methods Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls. Results Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared to 37 eyes in the control group (74%, p=1.0). Morphologically, the MacTel2 group trended towards having a higher proportion of pruning-type capillary dropout (44%) compared to controls (28%), but this was not statistically significant (p=0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared to controls (MacTel2 56%; Controls 42%; p=0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; Controls 10%; p=1.0), arteriovenous shunts (MacTel2 14%; Controls 18%; p=0.60), venous tortuosity (MacTel2 60%; Controls 66%; p=0.58), or arterial tortuosity (MacTel2 54%; Controls 68%; p=0.20), which was mild in the majority of cases. Conclusions We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using WFA. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.Summary SUMMARY:: We note a high incidence of peripheral retinal vascular findings in both patients with macular telangiectasis type 2 and age-matched controls. Patients with MacTel2 had significantly more microaneurysms compared to controls, independent of age or other systemic risk factors.

The development of non-invasive live ocular imaging and electrophysiological test systems for rodent eyes provides new tools for not only averaged analysis of the entire retina but also the ability to see, test, and compare different subregions of the same retina. These new capabilities provide the possibility for more detailed examinations of local structural and functional relationships within a single eye and the ability to also follow changes longitudinally over time. We have developed protocols based around the Micron-III/IV retinal imaging camera system for combining fluorescent imaging of the neural retinal micro-vasculature by FA (fluorescein angiography), imaging of all neural retinal layers by SD-OCT (Spectral-Domain Ocular Coherence Tomography), and focal “spot” light-targeted electroretinography (Focal-ERG) to relate the local neurovascular unit structure to the inner (photoreceptor) and outer-retinal electrical response to light stimulation. For demonstration purposes we have used the popular mouse oxygen induced retinopathy (OIR) model, which causes radial central patches of retinal neuron loss mostly in zones away from and between the primary retinal arteries and veins. In this model, the loss of central microvasculature is induced developmentally in mouse litters exposed to 75% oxygen from age P7 to P11. Return to room air on P12, causes several days of retinal ischemia during which neurons, mostly of the inner retina, perish. Bipolar and ganglion cell death ends as neovascular growth revascularizes the central retina. This model provides for non-uniform retinal damage as well as gradual progression and resolution over time. The OIR model was used to generate regions of inner retinal neuron loss in B6.Cg-TgThy1-YFP mice. Using image-guided focal-ERG, the dark-adapted mixed rod-cone light response was compared using stimulation of small circular (0.27 mm diameter) target areas located in the central retinas of the same eyes (OIR and control). The same areas of the same retinas were followed over three ages after revascularization (P21, P28 and P42).ConclusionsCombined FA and SD-OCT imaging can provide local geographic specific information on retinal structural changes and be used to select different retinal areas within the same eye for testing of local light response. This analysis strategy can be employed for studies with rodent disease models that do not uniformly impact the entire retinal area. Combining these techniques would also be useful for testing gene and cell replacement therapies in retinal degeneration models where typically a small zone of the retina is treated. Both treated and untreated retinal zones within the eye can be followed non-invasively over many weeks.SUMMARYMouse models utilized for retinal disease research including retinal vascular models can display nonuniform changes over the entire retina. Damage or loss of retinal layers and retinal neurons due to hypoxia can impact some retinal areas while leaving adjacent regions unaltered. Combining vascular imaging by fluoresceine angiography, vascular imaging and retinal layer imaging by SD-OCT, and focal-ERG provides us with new tools to examine retinal structure-function relationships within a single retina.

PURPOSE Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti-vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity. METHODS This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti-vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD. RESULTS Mean gestational age was 26 ± 2 weeks, and mean birth weight was 873 ± 341 g. Mean postmenstrual age on the day of injection was 35 ± 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4-335) after injection. Eleven percent detached within 1 week, 23% within 2 weeks, and 49% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29%, 4B in 37%, and 5 in 34% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = -0.54; P < 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86% of eyes. CONCLUSION Progressive atypical TRD may occur after anti-vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.

To determine the ocular hypertension (OHT) incidence in patients with a history of prematurity and the effect of intervention for acute retinopathy of prematurity (ROP) in infancy on OHT incidence.Retrospective case series at a single tertiary referral vitreoretinal practice.A total of 407 eyes of 213 patients were included, with ROP stage 0 to 5.A retrospective chart review was conducted of patients aged ≥15 years, seen from 1973 to 2013, with a history of premature birth (gestational age32 weeks). Data were collected from patient charts, including gender, date of birth, gestational age at birth, birth weight, stage of ROP at presentation, management (including laser, cryotherapy, lens-sparing vitrectomy [LSV], or lensectomy-vitrectomy). Ocular hypertension (if present) data included age of onset, timing of glaucoma surgery (if performed), lens status, and last follow-up examination.Development of OHT, defined as eyes requiring a glaucoma medication for more than 6 consecutive months or surgical intervention for elevated intraocular pressure.Of included eyes, 155 (38.1%) developed OHT within 69 years of follow-up. Subgroup analyses revealed an OHT incidence of 23.2% (36/155 eyes) in eyes without a history of any treatment for acute ROP (spontaneously regressed), 23.3% (10/43 eyes) in eyes that underwent ablative therapy alone, and 58.5% (76/130 eyes) in eyes requiring acute incisional retinal surgery (P0.01). Stage 4 eyes had a lower OHT incidence compared with stage 5 eyes (40.5% [17/42] vs. 66.7% [54/81], P0.01); however, among stage 4 and stage 5 eyes, phakic eyes at last follow-up had a decreased OHT incidence compared with aphakic eyes (27.8% [5/18] vs. 69.8% [60/86], P0.01).Patients with a history of extreme prematurity are at an increased risk of OHT and glaucoma, even if they did not receive acute ROP treatment. More severe acute ROP is associated with higher incidence of OHT, and this is associated with an increased incidence of incisional surgical intervention. Awareness of the increased lifelong risk of adverse ocular sequelae in patients with a history of prematurity will help guide appropriate monitoring.

Purpose To report the incidence of, and factors related to, glaucoma after lens-sparing vitrectomy (LSV) surgery in advanced retinopathy of prematurity (ROP). Design Retrospective case series at a single tertiary referral pediatric vitreoretinal practice. Participants Four hundred and one eyes from 270 patients were included. Methods The medical records of patients who underwent LSV for stage 4A, 4B, and 5 ROP were retrospectively reviewed. Data were collected from patient charts including gender, gestational age at birth, birthweight, stage of ROP at presentation, prior treatment (laser or cryotherapy), subsequent retinal surgeries, presence of glaucoma, time to glaucoma (interval between LSV and the onset of glaucoma), date of lensectomy (if performed), and retinal attachment status at last visit. Lensectomy was considered as a time-dependent covariate in the analysis. Main Outcome Measures Incidence of glaucoma and potential risk factors for time to glaucoma. Results Among 401 eyes with advanced ROP, 40 eyes (10.0%) had glaucoma during a mean of 3.06±4.11 years of follow-up. The incidence of glaucoma was 6.9% (17/247) in stage 4A, 12.0% (16/133) in stage 4B, and 33.3% (7/21) in stage 5 ROP. Twenty-one percent of eyes (87/401) required lensectomy at a mean of 1.23±2.19 years after LSV. In univariate analysis, having stage 5 ROP (vs. stage 4 ROP) and presence of lensectomy were found to be significantly associated with time to glaucoma (hazard ratio = 6.76, 95% confidence interval = 2.19–20.88, P = 0.001; hazard ratio = 3.06, 95% confidence interval = 1.56–6.0, P = 0.001, respectively). In multivariate analysis, lensectomy was the only significant independent factor associated with time to glaucoma (hazard ratio = 2.76, 95% confidence interval = 1.371–5.581, P = 0.004). Conclusions Patients with more severe ROP had a higher incidence of glaucoma after lens-sparing vitrectomy. If a patient required lensectomy owing to progression of ROP and/or presence of lens opacity, then the hazard of having glaucoma significantly increased compared with those without lensectomy.

The data presented in this article are related to the research paper entitled âNorrin treatment improves ganglion cell survival in an oxygen-induced model of retinal ischemiaâ (Dailey et al., 2017) [1] This article describes treatment with the human Norrin protein, an atypical Wnt-protein, to improve the survival of retinal ganglion cells in a murine model of Oxygen-Induced Retinopathy (OIR). That study utilized Optical coherence tomography (OCT) to visualize retinal layers at high resolution in vivo, and to quantify changes to nerve fiber layer thickness. Organization of the laminar structure of other retinal layers in this model in vivo, were not known because of uncertainties regarding potential artifacts during the processing of tissue for traditional histology. The OCT image data provided here shows researchers the retinal laminar structural features that exist in vivo in this popular mouse OIR model. Traditional H&E stained retinal tissue sections are also provided here for comparison. Keywords: Ocular coherence tomography, Retina, Oxygen-induced retinopathy, Mouse retina, Retinal imaging

Purpose: The purpose of this study was to conduct a bibliometric analysis to evaluate the publication trends of retinopathy of prematurity (ROP) literature over time, focusing on geographic and economic origins. Methods: A search for indexed English abstracts was performed in PubMed using search terms “retinopathy of prematurity” or “retrolental fibroplasia” from 1976 to 2015 and divided into 4 decades. Original research articles involving humans were included. Countries were grouped into high-, middle-, and low-income groups using World Bank criteria, and impact factors (IFs) were gathered from 2014 Thomson Reuters Journal Citation Reports. Results: A total of 5425 publications were identified, of which 2045 met the inclusion criteria. The ratios of publications per decade increased over time: 1976 to 1985 (5.4%), 1986 to 1995 (15.8%), 1996 to 2005 (25%), 2006 to 2015 (53.7%; Pearson r = .93, 95% confidence interval: 0.87-0.96). The rates of publications by income group were high—(82.2%), middle—(17.7%), and low—(0.1%). Respective mean (standard deviation) IFs by income group were 2.79 (4.87), 1.23 (1.17), and 0.42 (0.45). Top producing countries were the United States (37%), the United Kingdom (6.7%), India (4.6%), Japan (3.9%), and Turkey (3.5%). There was a significant difference between the time distribution of publications between high- and middle-income groups, where the latter has produced increasing publications in recent years ( P < .001), but in journals with lower IFs overall ( P < .001). Conclusions: Publications regarding ROP are increasing in number. Investigators from middle-income countries are increasingly contributing to the ROP literature but, overall, may not be recognized yet in journals with high IFs.

Purpose: To report the chorioretinal coloboma, and its association with increased risk of retinal detachment (RD) and choroidal neovascularization (CNV). Methods: This retrospective case series included eyes with chorioretinal coloboma diagnosed between 1995 and 2014 with a focus on RD and CNV as related complications. Cases of CNV were managed with laser photocoagulation or intravitreal injection of bevacizumab. For eyes with CNV, therapeutic success was defined as resolution of the subretinal hemorrhage on fundus examination and resolution of the subretinal and intraretinal fluid on optical coherence tomography (OCT). For eyes with RD, anatomic success following surgical intervention was defined as attachment of the retina at the last follow-up visit. Results: Fifty-one eyes of 31 patients with chorioretinal coloboma were identified for review. Bilateral chorioretinal coloboma was present in 64.5% of subjects. RD developed in 15 eyes (29.4%). Among 15 eyes with RD, 4 eyes (27%) had retinal breaks identified within the coloboma, 5 eyes (33%) had retinal breaks outside the coloboma, 2 eyes (13%) showed retinal breaks both inside and outside the coloboma, and in 4 eyes (27%) the causative retinal break was not localized. The overall rate of anatomic success after RD repair was 85.7%. CNV developed in 7 eyes (13.7%) and was located along the margin of the coloboma in all cases. CNV was bilateral in 2 of the 5 affected individuals (40%). Conclusion: RD and CNV were present in a high percentage of eyes with chorioretinal coloboma in these series. The frequent finding of retinal breaks outside the coloboma bed suggests that vitreoretinal interface abnormalities may play a role in development of RD in these eyes.

Purpose To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. Methods Observational case series involving single family and literature review. Results A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure. Laboratory work-up revealed severely shortened telomere length in both patients, and genetic testing revealed a missense mutation in the gene that encodes the reverse transcriptase component of telomerase, confirming the diagnosis of dyskeratosis congenita. The father of both children was a carrier of the same mutation, who exhibited marked retinal vascular tortuosity of the second-order vessels. Conclusion Dyskeratosis congenita is a severe multisystem disorder, which should be considered in cases of pediatric exudative retinopathies with concurrent signs and/or symptoms of bone marrow failure.

To describe the etiology and clinical characteristics of macular edema (ME) in patients with familial exudative vitreoretinopathy.Observational, retrospective case series of 30 patients (34 eyes) with ME and familial exudative vitreoretinopathy who underwent spectral-domain optical coherence tomography imaging between 2009 and 2016. Baseline and follow-up optical coherence tomographies were correlated with color fundus photography and fluorescein angiography.The average age was 20.6 years (6.6-68.7). Eighteen eyes exhibited cystoid ME (52.9%), 14 noncystoid ME (41.2%), and 2 eyes (5.9%) with both. Macular edema was foveal in 52.9% (n = 18). Eighteen of 24 eyes (64.3%) with an available fluorescein angiography showed leakage from ME. The most common structural feature was posterior hyaloidal organization/contraction (n = 15). Sixteen eyes were treated with topical or intravitreal steroids (n = 6), intravitreal anti-vascular endothelial growth factor (n = 3), or pars plana vitrectomy with membrane stripping (n = 7). There was no difference between mean preoperative and postoperative LogMAR visual acuity (0.63 [20/85] vs. 0.87 [20/148], P = 0.35) after vitrectomy despite a statistical improvement in the mean central foveal thickness (596 mm vs. 303 mm, P = 0.04).Macular edema in familial exudative vitreoretinopathy occurs most commonly because of traction. Vitrectomy is effective for relieving tractional forces with anatomical improvement.

Importance The US Food and Drug Administration’s medical device regulatory pathway was initially conceived with hardware devices in mind. The emerging market for ophthalmic digital devices necessitates an evolution of this paradigm. Objectives To facilitate innovation in ophthalmic digital health with attention to safety and effectiveness. Evidence Review This article presents a summary of the presentations, discussions, and literature review that occurred during a joint Ophthalmic Digital Health workshop of the American Academy of Ophthalmology, the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Cataract and Refractive Surgery, the American Society of Retina Specialists, the Byers Eye Institute at Stanford and the US Food and Drug Administration. Findings Criterion standards and expert graders are critically important in the evaluation of automated systems and telemedicine platforms. Training at all levels is important for the safe and effective operation of digital health devices. The risks associated with automation are substantially increased in rapidly progressive diseases. Cybersecurity and patient privacy warrant meticulous attention. Conclusions and Relevance With appropriate attention to safety and effectiveness, digital health technology could improve screening and treatment of ophthalmic diseases and improve access to care.

Purpose To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. Design International, multicenter, interventional, retrospective case series. Participants Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)—defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter—performed in both eyes sequentially during the same anesthesia session. Methods Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. Main Outcome Measures Ocular and systemic adverse events. Results A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [ P P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. Conclusions This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Capillary dropout is a common sequela of endothelial cell dysfunction that underlies the pathology of multiple retinal vascular diseases, including familial exudative vitreoretinopathy (FEVR). Wide-field fluorescein angiography allowed for identification of areas of capillary inflammatory changes and late-phase angiographic posterior and peripheral vascular leakage (LAPPEL). We propose LAPPEL as a precursor in pathogenesis of capillary dropout and a marker of endothelial cell inflammation in the retina. The authors describe a case of FEVR with significant macular edema associated with LAPPEL, which was successfully treated with topical and intravitreal steroids. The implication for disease mechanism and potential future treatment applications are also discussed. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:288–292.]

Purpose To determine if (1) tortuosity assessment by a computer program (ROPtool, developed at the University of North Carolina, Chapel Hill, and Duke University, and licensed by FocusROP) that traces retinal blood vessels and (2) assessment by a lay reader are comparable with assessment by a panel of 3 retinopathy of prematurity (ROP) experts for remote clinical grading of vascular abnormalities such as plus disease. Design Validity and reliability analysis of diagnostic tools. Participants Three hundred thirty-five fundus images of prematurely born infants. Methods Three hundred thirty-five fundus images of prematurely born infants were obtained by neonatal intensive care unit nurses. A panel of 3 ROP experts graded 84 images showing vascular dilatation, tortuosity, or both and 251 images showing no evidence of vascular abnormalities. These images were sent electronically to an experienced lay reader who independently graded them for vascular abnormalities. The images also were analyzed using the ROPtool, which assigns a numerical value to the level of vascular abnormality and tortuosity present in each of 4 quadrants or sectors. The ROPtool measurements of vascular abnormalities were graded and compared with expert panel grades with a receiver operating characteristic (ROC) curve. Grades between human readers were cross-tabulated. The area under the ROC curve was calculated for the ROPtool, and sensitivity and specificity were computed for the lay reader. Main Outcome Measures Measurements of vascular abnormalities by ROPtool and grading of vascular abnormalities by 3 ROP experts and 1 experienced lay reader. Results The ROC curve for ROPtool's tortuosity assessment had an area under the ROC curve of 0.917. Using a threshold value of 4.97 for the second most tortuous quadrant, ROPtool's sensitivity was 91% and its specificity was 82%. Lay reader sensitivity and specificity were 99% and 73%, respectively, and had high reliability (κ, 0.87) in repeated measurements. Conclusions ROPtool had very good accuracy for detection of vascular abnormalities suggestive of plus disease when compared with expert physician graders. The lay reader's results showed excellent sensitivity and good specificity when compared with those of the expert graders. These options for remote reading of images to detect vascular abnormalities deserve consideration in the quest to use telemedicine with remote reading for efficient delivery of high-quality care and to detect infants requiring bedside examination.

BACKGROUND AND OBJECTIVE: A retrospective clinical study was performed to assess whether photographically screened and remotely read images for retinopathy of prematurity (ROP) allowed for timely and accurate diagnosis of treatment-warranted ROP compared to bedside examination. PATIENTS AND METHODS: The study included 130 eyes of 65 premature neonates in born at William Beaumont Hospital, Royal Oak NICU. Bedside examined (2006 to 2010) and telemedicine screened (2010 to 2014) neonates were compared to identify whether there is a statistical difference in postmenstrual age (PMA) at the time of treatment. RESULTS: One hundred thirty eyes of 65 infants met the inclusion and exclusion criteria. Thirty-five infants who needed laser treatment were screened bedside with an average PMA at treatment of 36.5 weeks. Thirty infants who needed treatment were photographically screened, with an average PMA at treatment of 36.4 weeks. Neither group had statistically different PMAs ( P = .58). CONCLUSION: This study confirms that telemedicine also allows for appropriately timed treatment for early ROP. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e32–e35.]

Purpose We report a case of congenital toxoplasmosis associated with retinal detachment. Methods A 9-month-old white boy presented a unilateral tractional retina detachment associated with congenital toxoplasmosis retinochoroiditis. Results The diagnosis is supported by positive IgG (>400) for toxoplasmosis and intracranial calcification on magnetic resonance imaging, along with positive family history of Toxoplasma infection in the mother. Conclusion Tractional retinal detachment is an infrequent and unconventional presentation of congenital Toxoplasma infection. Inflammatory interference with normal sequence of vitreous development may explain pathogenesis of tractional retinal detachments in the setting of congenital ocular toxoplasmosis.

BACKGROUND AND OBJECTIVE: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time. PATIENTS AND METHODS: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease. RESULTS: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease ( P = .16), patient age ( P = .16), or presence of systemic vascular disease ( P = .16). CONCLUSIONS: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:221–227.]

Suprachoroidal hemorrhage (SCH) is a rare but serious complication that may accompany nearly any ocular surgery. In contrast to SCH in adults, the incidence and management of SCH in the pediatric population is poorly defined. Herein, the authors describe their experience managing SCH in patients of a younger age group, characterize this rare complication using multimodal imaging, and review the current literature on the subject. In this retrospective case series, two patients developed intraoperative SCH during cataract extraction once rendered aphakic. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:454–458.]

Purpose To describe the microstructural features of the macula and vitreomacular interface in persistent fetal vasculature syndrome (PFVS) with posterior involvement managed with early vitrectomy or with observation, with functional correlation. Methods We retrospectively identified 45 consecutive pediatric patients with PFVS with posterior involvement treated from 2005 to 2016. The eyes that could be imaged with spectral domain optical coherence tomography were included, and images were correlated with best-corrected visual acuity. Results Thirty-eight imaging sessions were performed on 10 eyes from 9 patients, including 7 that had been managed with vitrectomy for PFVS-related tractional retinal detachment, and 3 that had been observed. Mean age of the patients who were imaged was 9.1 years and their average length of follow-up was 5.9 years. Best-corrected visual acuities of the eyes imaged ranged from 20/30 to count fingers, with mean best-corrected visual acuity 20/163. All eyes imaged had microstructural anomalies identified. The main anomalous features included posterior hyaloidal organization, vitreoretinal traction, vitreopapillary traction, diminished foveal contour, foveal displacement, and disruption of the ellipsoid zone. Posterior hyaloidal organization (P = 0.043), diminished foveal contour (P = 0.019), and disruption of the ellipsoid zone (P = 0.014) were associated with worse best-corrected visual acuity. Conclusion Macular and vitreomacular interface anomalies were identified in all pediatric patients with posterior PFVS imaged with spectral domain optical coherence tomography. These microstructural findings, together with functional measures, may inform the diagnosis and management of PFVS with posterior involvement.

BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor (VEGF) therapy is increasing in popularity for treatment of retinopathy of prematurity (ROP). Despite many technical benefits, issues remain prompting further investigation. PATIENTS AND METHODS: Retrospective case report and literature review. RESULTS: A 42-week-old postmenstrual age female with gestational age of 28 weeks and birth weight of 990 g presented with prominent progression of peripapillary purely tractional atypical stage 4A ROP in both eyes following intravitreal bevacizumab therapy in the right eye only. CONCLUSION: The authors present the first reported case, to their knowledge, of a “crunch” phenomenon tractional retinal detachment from fellow eye administration of bevacizumab. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e102–e104.]

Purpose The in vivo microstructural features of familial exudative vitreoretinopathy (FEVR) have not been well described. We present new anatomic features of FEVR with functional and genetic correlations. Design Consecutive, retrospective, observational case series. Participants Patients with FEVR treated from 2009 to 2014. Methods We identified 346 patients with FEVR. Those imaged with spectral-domain optical coherence tomography (SD OCT) with or without enhanced depth imaging (EDI) were included, and images were correlated with best-corrected visual acuity (BCVA), widefield angiography, fundus autofluorescence (AF), and wnt signaling pathway mutations. Main Outcome Measures Exploratory SD OCT findings and BCVA. Results A total of 225 imaging sessions were acquired in 74 eyes from 41 patients. Mean age was 19.0 years. Sixty-seven eyes (91%) had interpretable images, of which 50 (75%) had anomalous microstructural findings; all eyes with FEVR severity of stage 2 or greater had abnormalities. A broad spectrum of features were identified: various forms of posterior hyaloidal organization, vitreomacular traction (VMT), vitreopapillary traction, vitreo-fold traction, vitreo-laser scar adhesion, diminished foveal contour, persistent fetal foveal architecture, cystoid macular edema (CME), intraretinal exudates and subretinal lipid aggregation, dry or edematous radial folds, and disruption of the ellipsoid zone. Mean foveal, central macular, and choroidal thicknesses were 305±145 μm, 337±160 μm, and 216±64 μm, respectively. In stages 1 to 2, greater foveal and central macular thicknesses ( Rho = 0.493, 0.544, respectively; both P Rho = 0.032; P = 0.868). Posterior hyaloidal organization ( P P P P P P P = 0.011) retained significance in multivariate modeling ( R 2 = 0.627; P Conclusions Spectral-domain OCT imaging identified microstructural anomalies in the majority of patients with FEVR.

Retinal cavernous hemangiomas are benign vascular anomalies that are typically unilateral and located outside of the macula. Fluorescein angiography findings include an early slow-filling, non-leaking lesion with late intermixed lobules of hyperfluorescence and hypofluoresence secondary to plasma and erythrocyte sedimentation. We present a novel case of unilateral macular cavernous hemangioma with bilateral peripheral vascular anomalies and nonperfusion. This may represent a phenotypic variation of hemangiomas that, in conjunction with recent histopathologic and genetic findings, may aid in future therapies for a disease that has been traditionally observed due to slow progression. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:764–767.]

Objective To describe the long-term effect of lens-sparing vitrectomy surgery for advanced retinopathy of prematurity (ROP) on lens clarity. Design Retrospective case series at a single tertiary referral pediatric vitreoretinal practice. Participants Four hundred ninety-six eyes from 351 patients were included. Methods A retrospective chart review was conducted of patients with diagnosis of ROP stage 4A, 4B, and 5 who underwent lens-sparing vitrectomy (LSV) between 1992 and 2013. Data were collected from patient charts, including gender, date of birth, gestational age at birth, birthweight, stage of ROP at presentation, initial treatment (laser or cryotherapy), date of LSV, date of lensectomy (if performed), lens status at time of lensectomy, date of last visit, lens status at last visit, subsequent retinal surgeries, and retinal attachment status at last visit. Patients were excluded if any surgery had been performed at an outside institution before referral, or if a scleral buckle had been placed. Eyes with a concurrent anatomic abnormality, such as coloboma or microcornea, or a known family history of familial exudative vitreoretinopathy (FEVR), were also excluded. Main Outcome Measures Retinal reattachment after LSV, lensectomy after LSV, lens opacity at the time of lensectomy, and lens clarity at last follow-up. Results Four hundred ninety-six eyes from 351 patients met inclusion criteria for this study. The reattachment rate after a single LSV surgery was 82.1% for stage 4A, 69.5% for stage 4B, and 42.6% for stage 5. Subsequent retinal surgeries were required in 19.8% of eyes, with 88.7% of them including a lensectomy. Among eyes requiring lensectomy, 75% occurred within the first year after LSV surgery. Lens opacities were present in 26.6% of eyes at the time of lensectomy. Of all eyes in this series, 5.9% required lensectomy because of lens opacity. Conclusions This study demonstrates that lens clarity is observed in most eyes after LSV surgery for advanced ROP for the patient's childhood. Within the first decade of life, if necessary, lensectomy after LSV occurred mostly within 1 year following LSV.

Purpose To describe the long-term anatomical and visual outcomes of a patient with retinopathy of prematurity characterized by a prominent retinal fold adherent to the posterior lens capsule, treated by lens-sparing vitrectomy with surgical transection of the retrolental membrane. Case summary A premature infant was born at a gestational age of 25 weeks and birthweight of 636 g. She developed threshold retinopathy of prematurity bilaterally and was subsequently treated with laser ablative therapy. The left eye responded favorably, with regression of neovascularization; however, the right eye progressed to Stage 4A with a prominent retinal fold adherent to the posterior lens capsule. The patient underwent lens-sparing vitrectomy with dissection of the retrolental membrane at postmenstrual age of 44 weeks. At 15-year follow-up, the patient has maintained a best-corrected visual acuity of 20/60 and, of note, demonstrated complete resolution of the previous retinal fold. Conclusion Surgical treatment for retinopathy of prematurity was considerably advanced by the introduction of lens-sparing vitrectomy techniques; however, cases developing retrolental membranes often persisted with poor visual outcomes, and lensectomy is conventionally performed. However, in select cases of Stage 4A retinopathy of prematurity, careful transection of retrolental membranes during lens-sparing vitrectomy using the appropriate technique may provide very good anatomical and visual outcomes.

To discuss the latest advances and controversies in the diagnosis and care of infants with retinopathy of prematurity (ROP).Literature review.Retinopathy of prematurity remains a major global issue. Industrialized nations now treat profoundly premature infants with posterior and aggressive disease, and middle-income nations are experiencing ROP epidemics. Remote digital imaging may address the decreasing ratio of ROP providers to premature infants, in addition to improving patient care. Widefield angiography, optical coherence tomography, and the Wnt signaling pathway have provided new insights into ROP pathogenesis. Anti-vascular endothelial growth factor treatment is increasing in popularity, but the dearth of information to guide dosing, unpredictable reactivation, persistent vascular abnormalities, the "crunch" phenomenon, and the presently unknown effects of systemic vascular endothelial growth factor suppression remain issues to continue investigating. Neurodevelopmental delay has been raised as a potential consequence, but the evidence currently is weak. Vitrectomy is the treatment of choice for Stages 4 and 5. Illumination techniques, ab interno incisions, plasmin-assisted vitrectomy, staged surgery in the interest of corneal clearing for advanced Stage 5, and immediate sequential bilateral vitreoretinal surgery, are useful techniques.We are making progress in ROP management. Our goal as clinicians is to continue expanding the boundaries of our abilities to keep this blinding disease in check globally.

Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of prematurity, bedside examination with binocular indirect ophthalmoscopy has been the gold standard technique for screening, yet with several limitations. Herein, we review the current evidence that supports the role of telemedicine for the screening of infants with retinopathy of prematurity.

Purpose To evaluate the long-term outcomes of treatment of total exudative retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of vitrectomy. Design Retrospective, observational case series. Participants A total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to Coats disease with at least 5 years of follow-up. Methods We reviewed the records of patients with stage 3B Coats disease. The interventions, including the timing of vitrectomy if used, and clinical course were recorded. Main Outcome Measures The primary outcome measures were visual acuity at the most recent appointment, whether there was progression to neovascular glaucoma (NVG) or phthisis bulbi, and need for enucleation. Results All patients received ablative treatment (photocoagulation or cryotherapy), with 8 having scleral buckling (SB) and 6 having external drainage of subretinal fluid (XD). Of the 12 patients who had pars plana vitrectomy (PPV), 8 had early PPV (EV) in the first year after presenting, and 4 of 8 in the expectant management group had late PPV (late vitrectomy) at a mean of 4.3 years post-presentation for treatment of significant traction retinal detachment (TRD). The other 4 patients of 8 in the expectant management group did not require vitrectomy. Mean follow-up overall was 9 1/2 years. At the date of last follow-up, 50% had no light perception or light perception vision, which was consistent across the subgroups that underwent EV (4/8), late vitrectomy (2/4), or no PPV (2/4). A total of 4 of 16 patients had progression to NVG or phthisis, 1 of whom required enucleation. Conclusions In this retrospective series of patients with Stage 3B Coats disease, ablative therapy with a combination of PPV, XD, or SB was effective in preventing progression to NVG or phthisis in the majority of patients, thus preserving the globe. Half of the patients (4/8) in this series who did not undergo PPV in the early vitrectomy group developed late-onset TRD, suggesting a possible role for early prophylactic vitrectomy with possible SB and XD; however, this is balanced by the other half (4/8) in the expectant management group who did not require any vitrectomy.

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.ResultsThere were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.ConclusionPaediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.

Treatment of a mouse model of oxygen-induced retinopathy (OIR) with recombinant human Norrin (Norrie Disease Protein, gene: NDP) accelerates regrowth of the microvasculature into central ischemic regions of the neural retina, which are generated after treatment with 75% oxygen. While this reduces the average duration and severity of ischemia overall, we do not know if this accelerated recovery of the microvasculature results in any significant survival of retinal ganglion cells (RGCs). The purpose of this study was to investigate ganglion cell survival with and without the intravitreal injection of Norrin in the murine model of oxygen induced retinopathy (OIR), using two strains of mice: C57BL/6J and Thy1-YFP mice. Intravitreal injections of Norrin or vehicle were done after five days of exposure to 75% oxygen from ages P7 to P12. The C57BL/J mice were followed by Spectral-Domain Optical Coherence Tomography (SD-OCT), and the average nerve fiber layer (NFL) and inner-plexiform layer (IPL) thicknesses were measured at twenty-four locations per retina at P42. Additionally, some C57BL/J retinas were flat mounted and immunostained for the RGC marker, Brn3a, to compare the population density of surviving retinal ganglion cells. Using homozygous Thy1-YFP mice, single intrinsically fluorescent RGCs were imaged in live animals with a Micron-III imaging system at ages P21, 28 and P42. The relative percentage of YFP-fluorescent RGCs with dendritic arbors were compared. At age P42, the NFL was thicker in Norrin-injected OIR eyes, 14.4 μm, compared to Vehicle-injected OIR eyes, 13.3 μm (p = 0.01). In the superior retina, the average thickness of the IPL was greater in Norrin-injected OIR eyes, 37.7 μm, compared to Vehicle-injected OIR eyes, 34.6 μm (p = 0.04). Retinas from Norrin injected OIR mice had significantly more surviving RGCs (p = 0.03) than vehicle-injected mice. Based upon NFL thickness and counts of RGCs, we conclude that Norrin treatment, early in the ischemic phase, increased the relative population density of surviving RGCs in the central retinas of OIR mice.

Purpose The tractional retinoschisis is a poorly understood, rare, and likely underappreciated entity in retinopathy of prematurity. The purpose of this article is to describe clinical findings and surgical management of tractional retinoschisis in retinopathy of prematurity, masquerading as Stage 4 retinopathy of prematurity retinal detachment. Methods A retrospective review of a single case with literature review and case discussion. Results In this report, we describe a child with retinopathy of prematurity and tractional schisis, who initially presented with vitreous hemorrhage and was effectively managed by vitrectomy and inner wall retinectomy. At 5 months after vitrectomy, the child demonstrated complete collapse of the retinoschisis with intact posterior pole and brisk light perception. Conclusion Vitrectomy with or without inner wall retinectomy is effective in the management of tractional retinoschisis.

Purpose To describe the diversity of clinical findings associated with familial exudative vitreoretinopathy (FEVR) using wide-field angiography and to update the current classification system. Design Retrospective case series at a single tertiary referral vitreoretinal practice. Participants A total of 174 eyes of 87 subjects were studied. Methods A retrospective chart review was conducted of patients with a diagnosis of FEVR between January 2011 and January 2013 at a single tertiary care retina practice. Data were collected from patient charts, including sex, gestational age at birth, age at presentation, referring diagnosis, family history, prior ocular surgery, clinical presentation, and diagnostic imaging in each eye. Inclusion criteria included clinical diagnosis of FEVR in patients referred to our clinic for evaluation of decreased vision. Patients were excluded if a diagnosis of FEVR could not be made. Main Outcome Measures Clinical and angiographic findings. Results A total of 87 subjects met the inclusion criteria for this study. A broad spectrum of previously undescribed clinical and angiographic findings were associated with FEVR on wide-field angiography. These findings can be grossly divided into anatomic and functional changes. Anatomic changes include aberrant circumferential peripheral vessels, venous and arterial tortuosity, late-phase disc leakage, central and peripheral telangiectasias, capillary anomalies, and capillary agenesis. Functional changes include venous-venous shunting, delayed arteriovenous transit, and delayed or absent choroidal perfusion on fluorescein angiography. Conclusions Familial exudative vitreoretinopathy has a wide range of unrecognized or under-recognized clinical and angiographic findings that are easily identified using wide-field fluorescein angiography. These novel findings have led to an update of the original FEVR classification scheme and more complete characterization of early stages of FEVR.