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OBJECTIVE: This study evaluates the 24 month follow up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score

Background In autoimmune myasthenia gravis (MG), autoantibodies target the neuromuscular junction. Ocular myasthenia gravis (OMG) is localized, affecting only extraocular and/or levator palpebrae muscles. OMG presents across all ages, varying in presentation, treatment modalities, and outcomes. Recently, there have been advances in MG/OMG treatment; their utilization and effectiveness are an important part of optimal disease management. Methods We completed a retrospective chart review of children aged 18 years or younger with a confirmed diagnosis of OMG presenting from 2002 to 2019. Results Forty-two patients were included with mean age at presentation of 8.5 years (2 to 18 years). Twenty-one patients (50%) had positive antibodies; 90% had acetylcholine receptor antibodies. Ten patients developed generalized symptoms with mean time to generalization of 13.6 months. Multiple logistic regression showed that older age of onset was a trend predictive factor (P = 0.054; odds ratio 1.17) for generalized disease. All patients were treated with pyridostigmine. Immunomodulating agents included steroids (15), mycophenolate mofetil (four), and intravenous immunoglobulin (one). Three patients underwent thymectomy. Twenty patients reached minimal manifestation status, and 12 achieved remission. Gender, race, and positive antibody status were not statistically significant predictors for advanced immunosuppressive therapy. Conclusions We summarize one of the largest cohorts of pediatric patients with OMG who have undergone up-to-date diagnostic and therapeutic regimens. The predictors of outcome and treatment pathway for OMG patients suggested by this report may be further elucidated by future prospective studies.

Importance Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. Objective To find the lowest dose of intravitreous bevacizumab effective for severe ROP. Design, Setting, and Participants Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. Interventions Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. Main Outcomes and Measures Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg. Conclusions and Relevance These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.

Purpose To evaluate the development of cataracts or elevated intraocular pressure (IOP) in patients with Duchenne muscular dystrophy (DMD) on long-term glucocorticoid (GC) treatment. Methods The medical records of DMD patients evaluated from 2010 to 2015 at a single center were reviewed retrospectively. The main outcome measures were prevalence of cataracts and elevated IOP, age of first detection of cataract, time from initial steroid use to first detection of cataract, and relative risk of cataract development for deflazacort versus prednisone treatment. Results Of 596 DMD patients, 514 underwent GC therapy; all but one was male. The racial distribution was 82.1% white, 1.0% African American, 5.0% Hispanic, 2.9% Asian, and 8.0% more than one race or “other.” The prevalence of cataracts was 22.4% in patients on GC therapy. The mean age at which cataract formation was first documented was 12.9 ± 4.1 years (IQR, 9.6-14.6). The mean time from initial steroid use to the first detection of cataract was 6.5 ± 3.6 years (IQR, 4.0-8.6). The odds of cataract development were 2.4-fold higher for patients on deflazacort compared with prednisone (95% CI, 1.3-4.5; P = 0.004). Only 7 patients (1.4%) underwent cataract surgery, at a mean age of 16.9 years (range, 10.7-24.6 years); all were on deflazacort. Among patients with available intraocular pressure measurements, elevated IOP occurred in only 1 patient (1.1%), who was on deflazacort. Conclusions In patients undergoing GC therapy for DMD, the rate of cataract formation was slow and well tolerated, with a higher risk among deflazacort patients. The percentage of patients requiring cataract extraction or with elevated IOP was very small. These findings suggest that a schedule of annual eye examinations is appropriate.

Purpose To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. Methods A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. Results Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1 article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). Conclusions Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects.

Objective To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP. Methods A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories—model development and model validation—and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence. Results In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants. Conclusions Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations.

Importance The first Postnatal Growth and Retinopathy of Prematurity Study (G-ROP-1) developed new screening criteria with 100% sensitivity for type 1 retinopathy of prematurity (ROP) and 30% reduction of infants requiring examinations in a retrospective development cohort of 7483 infants from 29 North American hospitals in 2006-2012. Infants meeting 1 or more of the following criteria undergo examinations: gestational age less than 28 weeks or birth weight less than 1051 g; weight gain less than 120 g during age 10 to 19 days, weight gain less than 180 g during age 20 to 29 days, or weight gain less than 170 g during age 30 to 39 days; or hydrocephalus. Objective To evaluate the generalizability of the G-ROP screening criteria in a new cohort of at-risk infants. Design, Setting, and Participants This prospective validation cohort study (G-ROP-2) was conducted at 41 hospitals in the United States and Canada (25 G-ROP-1 hospitals and 16 new hospitals) from September 8, 2015, to June 13, 2017, among 3981 premature infants at risk for ROP and with known ROP outcomes. Main Outcomes and Measures Sensitivity for Early Treatment for Retinopathy of Prematurity Study type 1 ROP and potential reduction in infants receiving examinations. Results Among the 3981 infants in the study (1878 girls and 2103 boys; median gestational age, 28 weeks [range, 22-35 weeks]; median birth weight, 1072 g [range, 350-4080 g]; 1966 white; 942 black; 321 Latino; 120 Asian; 22 Native Hawaian or Pacific Islander; and 25 American Indian or Alaskan Native), the G-ROP criteria correctly predicted 219 of 219 cases of type 1 ROP (sensitivity, 100%; 95% CI, 98.3%-100%), while reducing the number of infants undergoing examinations by 35.6% (n = 1418). In a combined G-ROP-1 and G-ROP-2 cohort of 11 463 infants, the G-ROP criteria predicted 677 of 677 cases of type 1 ROP (sensitivity, 100%; 95% CI, 99.4%-100%), reducing the number of infants receiving examinations by 32.5% (n = 3730), while current criteria (birth weight Conclusions and Relevance This study found that the G-ROP screening criteria were generalizable on validation and, if used clinically in the United States and Canada, could reduce the number of infants receiving examinations. The large G-ROP cohorts provide evidence-based screening criteria that have higher sensitivity and higher specificity (fewer infants receiving examinations) for type 1 ROP than currently recommended guidelines.

Purpose To determine the prevalence and characteristics of eyes treated for retinopathy of prematurity (ROP) not meeting currently recommended early treatment (type 1) criteria. Methods This was a secondary analysis of data from the Postnatal Growth and ROP (G-ROP) Study, a retrospective cohort study of 7,483 infants undergoing ROP examinations and treatment at 29 North American hospitals between January 2006 and June 2012. Medical records were reviewed to determine the prevalence and characteristics of eyes treated for ROP less severe than type 1 ROP. Results Of 1,004 eyes that received ROP treatment, 126 eyes of 91 infants (0.8% of all eyes; 12.5% of treated eyes) underwent treatment for ROP less severe than type 1. Mean age at treatment was 38 weeks’ post-menstrual age (range, 32-49 weeks). Reasons for treatment included type 1 ROP in the fellow eye (43%), stage 3 ROP with pre-plus in the treated eye (30%), concerning structural changes in the retina (7%), persistent stage 3 ROP for ≥6 weeks without regression (6%), stage 3 ROP with no plus disease in the treated eye (5%), stage 3, zone III ROP with plus disease (3%), logistical considerations (3%), or stage 2 disease in the treated eye (2%). Conclusions Of all eyes treated for ROP, 1/8 were treated for disease less severe than currently recommended type 1 criteria. Clinician judgment of risk for permanent vision impairment superseded recommended treatment criteria and was usually related to type 1 disease in the fellow eye or pre-plus vascular changes in one or both eyes.

Importance Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. Objective To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Design, Setting, and Participants Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles. Interventions Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Main Outcomes and Measures Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. Conclusions and Relevance A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.

Our previous study demonstrated that topical ocular instillation can deliver effective concentrations of propranolol in the periocular tissues, and may be superior to oral propranolol in the treatment of periocular capillary hemangiomas. The objective of this study was to investigate the effects of dosing protocol on the distribution of propranolol in the periocular tissues and plasma after topical ocular instillation.Each rabbit received propranolol 0.5% ophthalmic solution using one of the following dosing protocols: three drops of 50 μL, one drop of 50 μL, or one drop of 25 μL. The periocular tissues (e.g. eyelids and extraocular muscles) and blood were collected and assayed for propranolol at 1 h after dosing.Decreasing the concentration of eye drops (1% to 0.5%), decreasing the number of eye drops during dosing (three drops to one drop), or decreasing the instilled volume (50 µL to 25 µL) generally lowered the concentration of propranolol in the periocular tissues. Nevertheless, therapeutic levels of propranolol ( 0.4 μg/g) were delivered to the periocular tissues at 1 h after dosing using any of the three protocols examined. Dose-dependent concentrations in some periocular tissues and plasma were observed over the dose range of 0.125 mg to 1.5 mg. The plasma concentration of propranolol was not measurable when a single 25 μL of propranolol 0.5% was instilled in the eye.The dosing protocol of topical ocular instillation can be tailored to achieve the desired therapeutic concentrations of propranolol in the periocular tissues while minimizing systemic exposure.

Purpose Fetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP). Design Single-center, retrospective cohort study. Participants We included a total of 343 premature infants (401-1250 g birth weight [BW], from 1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated. Methods For each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed. Main outcome measures Association of ADL during early gestation with SROP. Results In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively. Conclusions Higher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during early gestation to decrease the risk of SROP.

IMPORTANCE: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. OBJECTIVE: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks’ gestational age. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial included 638 infants younger than 28 weeks’ gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. INTERVENTIONS: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. MAIN OUTCOMES AND MEASURES: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. RESULTS: Among 638 infants (mean, 26 weeks’ gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks’ postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). CONCLUSIONS AND RELEVANCE: Among premature infants younger than 28 weeks’ gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Objective To evaluate the severity of postoperative inflammation, degree of patient discomfort, adequacy of wound closure, and length of operating time when using fibrin glue compared with sutures to close limbal conjunctival incisions after strabismus surgery. Methods Literature searches of the PubMed and Cochrane Library databases were last conducted on January 24, 2013, and resulted in 24 citations, including 2 not in the English language. All citations were reviewed in full text. Five studies compared fibrin glue (68 eyes) with sutures (74 eyes) for closure of limbal conjunctival incisions in patients undergoing strabismus surgery and were included in this assessment; no studies were found that evaluated fornix incisions. A quality rating was assigned to each study using criteria specifically developed for this assessment. Results No level I studies were found, and 5 level II studies were identified. There was significantly less postoperative inflammation and patient discomfort for 1 to 3 weeks after strabismus surgery for eyes treated with fibrin glue compared with sutures. In 3 studies that evaluated wound apposition, 2 of 50 eyes (4%) with conjunctival incisions that were initially closed using fibrin glue subsequently developed a wound gap that required suture repair. In the 2 studies that compared surgical time, fibrin glue required 1 to 5 minutes less time than suturing in 1 study and 55% less time (3.8 vs. 8.4 minutes) in a second study. These 5 studies did not evaluate the cost-effectiveness or risk of viral transmission from fibrin glue. Conclusions Studies in the literature suggest that the off-label use of fibrin glue to close limbal conjunctival incisions in strabismus surgery resulted in less postoperative inflammation and required shorter operating time compared with sutures, but it increased the percentage of wounds requiring subsequent repair with sutures. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To compare intraocular pressure (IOP) measurements in children 18 years of age and younger using rebound tonometry and applanation tonometry and the feasibility of using these techniques in children. Methods Literature searches of the PubMed and the Cochrane Library databases were last conducted in June 2012 and resulted in 43 citations, including citations not in English. Of these 43 citations, 4 studies met the inclusion criterion following full text review. A level of evidence rating was assigned to each study using criteria specifically developed for this assessment. Results No level I study was found in the literature search, and 2 level II and 2 level III studies were identified. Intraocular pressure was 2 to 3 mmHg higher using rebound tonometry compared with Goldmann applanation tonometry in the 2 level II studies performed in a clinic setting and in 1 level III study performed on children under general anesthesia. However, IOP was lower in 1 level III study in which noncontact applanation tonometry was compared with rebound tonometry. Bland-Altman plots showed that the difference in IOP for rebound versus Goldmann applanation tonometry increased as the IOP increased. The success rate for measuring IOP was markedly higher in children 3 years of age and younger using rebound tonometry compared with noncontact tonometry in 1 level III study. Conclusions Rebound tonometry seems to be a reasonably accurate instrument that allows the IOP to be measured in many children without using general anesthesia. More data are required to assess better how the differences between instruments vary with IOP measurement. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinopathy of prematurity (ROP) is a proliferative disorder involving the developing vasculature of premature infants that can result in retinal detachment and blindness. Timely screening for ROP and prompt treatment of severe ROP can decrease the prevalence of unfavorable retinal structural and poor visual outcome. The criteria for treatment of ROP has evolved from classic threshold ROP, as defined in the Multicenter Trial of Cryotherapy for ROP, to type 1 prethreshold ROP, as defined in the Early Treatment of ROP randomized trial, with incremental improvement in the overall treatment outcome. The mode of treatment has also transitioned from the use of cryotherapy to laser photocoagulation. The mouse model of oxygen-induced retinopathy has elucidated the pathogenesis of ROP and led to new interventions and screening approaches. Pharmacotherapy using the intravitreal injection of bevacizumab, an antibody to vascular endothelial growth factor, appears to be superior to laser photocoagulation for type 1 ROP in zone I but equivalent to laser therapy for type 1 ROP in zone II. However, the systemic risks associated with bevacizumab are uncertain. New screening algorithms based on the rate of postnatal growth of at risk infants are being developed in order to reduce the percentage of infants screened while maintaining efficacy. Digital fundus photography has a high degree of accuracy for the detection of treatment warranting ROP. Validation studies for the reliability and accuracy of telemedicine for ROP are under way.

Objective To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Methods Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Results Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Conclusions Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Oral propranolol has become a promising treatment of capillary hemangiomas (CHs) despite concerns of side effects associated with systemic beta-blockers. The objective of this study was to investigate the distribution of propranolol in periocular tissues and in plasma after topical application of propranolol as compared with intravenous and oral administration of propranolol.Each rabbit received propranolol as ophthalmic solution (1%) in one eye (1.5 mg dose), intravenous injection (1.5 mg dose), or commercially available propranolol oral solution (5 mg dose). The periocular tissues (e.g., eyelids and extraocular muscles) and blood were collected and assayed for propranolol.After topical instillation of 1.5 mg propranolol, high amounts of propranolol were rapidly delivered to the eyelids and extraocular muscles (4-32 μg/g at 1 h after dosing). The drug in these tissues was slowly cleared, and significant amounts of the drug (0.4 μg/g) were still present at 24 h after the topical application. After oral administration of a clinically relevant dose of 5 mg propranolol, the drug concentrations in the periocular tissues were relatively low (0.4 μg/g) at 1 h after dosing and generally undetectable at 8 h after dosing. After an intravenous injection of 1.5 mg propranolol, the drug concentrations in the eyelids and extraocular muscles were in the range of 0.2-1 μg/g at 1 h after dosing. The plasma concentration of the drug after the intravenous injection was significantly higher than that after topical application of the same dose. The higher drug concentrations in the periocular tissues of the treated eyes as compared with untreated eyes suggest direct penetration of the drug into the periocular tissues from the administration site after topical application.Topical administration can provide increased concentrations of propranolol in the periocular tissues and, thus, is superior to systemic administration for the treatment of periocular CH.

Purpose To determine whether a multivariate risk model can select infants with low-risk eyes for an alternative protocol that reduces retinopathy of prematurity (ROP) screening without loss of effectiveness. Methods This was a retrospective, nonrandomized, comparative study. We assigned 712 eyes of 357 premature infants of 401–1,250 g birth weights as high or low risk for prethreshold or threshold ROP using a risk model with variables of birth weight, gestational age, multiple birth, race, and gender. Using simulations, infants with high-risk eyes ( p ≥ 0.15) were screened conventionally, while those with low-risk eyes were screened with the 35q3 protocol (initial examination at 35 weeks postmenstrual age followed by screening every 3 weeks, with increased or decreased intervals based on ROP severity). The resultant reduction in ROP screening and the delay to detection of severe ROP were calculated. Results The 35q3 protocol reduced the mean number of eye examinations per infant in the overall population by 13.4% ( p = 0.0051). No eyes had a delay to the detection of threshold or type 1 zone 1 ROP. Of a total of 57 type 1 ROP eyes, 2 eyes with type 1 zone 2 ROP were delayed to detection by 1 week. As our study was done prior to the Early Treatment of ROP study, the 2 eyes were observed and regressed without progression to threshold ROP. Conclusions A risk-based alternative screening protocol increased the efficiency of ROP screening for infants of 401–1,250 g birth weight without an apparent loss of effectiveness. This investigational approach requires further validation by multicenter studies.

Background: The aim of this study was to determine the concentrations of propranolol in periocular tissues and plasma after ocular instillation of 0.5% propranolol gel-forming solution (GFS) as compared to 0.5% propranolol non-gelforming solution (non-GFS) for potential use in the treatment of periocular capillary hemangiomas. Methods: A GFS prepared in 1% sodium alginate or a non-GFS in phosphatebuffered saline was instilled into the eyes of rabbits. At predetermined time intervals after dosing, blood was withdrawn, rabbits were euthanized, and periocular tissues were dissected. Results: Ocular instillation of the GFS resulted in higher concentrations of propranolol in the outer layers of both the upper and lower eyelids (in the range of 9.9-36.9 μg/g) and maintained higher levels of propranolol in these tissues for 24 h after dosing, as compared to the ocular instillation of the non-GFS (in the range of 3.4-15.1 μg/g). While the concentrations of propranolol in the other periocular tissues were generally similar for GFS and non-GFS at 1 h after dosing, the concentrations of propranolol in the extraocular muscles and periocular fat were higher for GFS than those for non-GFS between 4-24 h after dosing. Lower level of propranolol in plasma was observed at 1 h with GFS as compared with non-GFS. Conclusion: The use of the propranolol gel-forming solution can prolong drug retention on the ocular surface and increase its distribution to the outer layers of the eyelids while decreasing systemic exposure to the drug.

Purpose: To assess anatomic outcomes following repair of traumatic retinal detachment (RD) among a cohort of cognitively impaired adolescents with self-injurious behaviors. Methods: Main outcome measures in this retrospective, consecutive, interventional case series were retinal attachment and postoperative complications. Results: Complete retinal reattachment was initially achieved in all 9 eyes of 9 patients. Six (67%) eyes had chronic RD at initial presentation, and 7 (78%) patients had limited vision from inoperable RD in the fellow eye. Proliferative vitreoretinopathy led to recurrent RD in 4 (44%) eyes at a mean of 2.7 months. Final total or partial retinal attachment was achieved in 6 (67%) and 3 (33%) eyes, respectively, with a mean of 1.7 procedures over a mean follow-up of 22.4 months. Silicone oil emulsification led to progressive glaucoma in 4 (50%) of 8 eyes in which it was used, requiring silicone oil exchange (2 eyes) or removal (2 eyes). Recurrent RD developed in both eyes from which silicone oil was removed despite prior retinal anatomic stability for more than 6 months. Conclusion: Cognitively impaired adolescents with self-injurious behaviors typically presented with severe visual impairment from chronic traumatic RD in one or both eyes. Despite initial anatomic success, formation of proliferative vitreoretinopathy and further ocular trauma from continued self-injurious behaviors led to a high rate of recurrent RD. Long-term silicone oil tamponade may prevent recurrent RD in this challenging scenario but is associated with vision loss from progressive glaucoma and corneal decompensation.

Purpose To report on a series of patients who developed orbital myositis following routine strabismus surgery. Methods A retrospective medical record review of patients who developed myositis following routine strabismus surgery. Surgery was performed on all patients between 1998 and 2003 by a single pediatric ophthalmologist (SMA). Results Four patients developed orbital myositis following routine strabismus surgery. All four cases were reoperations. Symptoms of myositis developed at a mean of 21 days after surgery (range, 4-34). In the initial patient, the diagnosis of myositis was based on clinical and computed tomography findings. The clinical course of the three subsequent patients was similar to that of the radiologically confirmed case. In all cases, the diagnosis was supported by rapid resolution after treatment with systemic corticosteroids. Conclusions Orbital myositis is a previously unreported complication of strabismus surgery. Reoperation appears to be a predisposing factor.

Purpose To characterize the results of vertical rectus muscle recession, or recession and resection surgery for vertical abnormal head posture (VAHP) due to null-point nystagmus. Method This is a retrospective, noncomparative, consecutive case series of patients who underwent vertical rectus muscle recession alone, recession then resection, or combined recession/resection surgery for VAHP due to null-point nystagmus. The primary outcome measure was the amount of residual VAHP. Results Twenty patients with VAHP due to null-point nystagmus were studied. The mean follow-up interval after surgery was 49 months (median: 44 months; range 9 to 124 months). Preoperative VAHP ranged from 10° to 45°, and the total amount of bilateral vertical rectus muscle recession, or recession and resection surgery, ranged from 8.5 to 20.0 mm per eye. After recession alone, 5/11 had residual VAHP ≤ 5°. The remaining six underwent subsequent resection or plication for residual VAHP > 10° that resulted in residual VAHP ≤ 5° in each case. After combined recession/resection, 6/9 had residual VAHP ≤ 5° and the remaining three had VAHP Conclusion Large amounts of vertical rectus muscle surgery are indicated to successfully correct the VAHP associated with nystagmus with a vertical null point. Combined recession/resection of the appropriate vertical rectus muscles, instead of recession alone, appears to be a more effective procedure.