Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

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.

Resident and fellow participation in strabismus surgery: effect of level of training and number of assistants on operative time and cost.

OBJECTIVE: To investigate the effect of the level of training and number of assistants on operative time for uncomplicated, 2-muscle, horizontal strabismus surgery at an academic institution. DESIGN: Comparative case series. PARTICIPANTS: A total of 993 children and adults between the ages of 6 months and 75 years. METHODS: Retrospective chart review of strabismus surgeries performed between July 1, 2008, and December 31, 2012, by any of 3 attending surgeons assisted by a resident in the postgraduate year 3 (PGY3), fellow in the postgraduate year 5 (PGY5), or both. MAIN OUTCOME MEASURES: Operative time (minutes) and associated operative cost (dollars). RESULTS: There were 373 cases with 1 assistant and 44 cases with 2 assistants. Of all cases with 1 assistant, there were 200 cases with a PGY3 assistant an average operative time of 62.5 minutes (standard deviation [SD], 15.1) and 173 cases with a PGY5 assistant an average operative time of 59.0 minutes (SD, 14.7); the difference of 3.5 minutes was statistically significant (P = 0.02). The average operative time for all cases with 2 assistants (both PGY3 and PGY5) was 10.6 minutes longer than all cases with 1 assistant (P = 0.0002). No statistically significant variation in operative times was demonstrated when comparing cases with a PGY3 (P = 0.29) and PGY5 (P = 0.44) assistant in their respective first and last halves of the academic year, but operative times within individual quarters of the academic year were significant for PGY3 (P = 0.03) but not for PGY5 (P = 0.24) assistant cases. Operative times were significantly different for individual PGY3 (P = 0.03) but not PGY5 (P = 0.22) assistant cases. Cost per PGY3 assistant per year for additional operative time is $3141.95. CONCLUSIONS: Operative time in strabismus surgery increased with PGY3 participation and further increased with both assistants over either assistant alone. Operative times earlier in the year did not vary from those later in the year for PGY3 or PGY5 assistants. The difference in quarterly and individual PGY3 but not PGY5 assistant operative times suggests that efficiency in strabismus surgery varies by assistants with less experience or interest.

Ventriculoperitoneal shunt as a treatment of visual loss in idiopathic intracranial hypertension.

BACKGROUND: The aims of this study were to evaluate visual function outcomes in idiopathic intracranial hypertension (IIH) patients who underwent ventriculoperitoneal (VP) shunt for visual loss and to determine a VP shunt survival curve over time. METHODS: A retrospective medical record review was performed of all new IIH patients first evaluated at our institution who underwent VP shunt placement over a 7-year period (2004-2010). There were 2 primary outcome measures: the first being visual acuity (VA) and the second being shunt survival. Patients who received VP shunt for visual loss were included in the visual outcome analysis, and all patients who received VP shunt for any reason were included in the shunt survival analysis. RESULTS: Of the 338 new patients with IIH, 19 patients (6%) met the inclusion criteria and 17 underwent VP shunt for visual loss and 2 for headaches. Average follow-up was 21.2 months (range, 5-1,342 days). Of the 17 patients who had VP shunt for visual loss, 5 patients had optic nerve sheath fenestration (ONSF) surgery before VP shunt, and 1 patient had bilateral ONSF surgery after VP shunt. Median VA before shunt was 20/200 in the worse eye (range, 20/20 to NLP) and 20/40 in the better eye (20/20 to HM). Median VA after shunt was 20/60 in the worse eye (20/20 to lumboperitoneal) and 20/30 in the better eye (20/20 to 20/800). The improvement in VA was statistically significant in both worse eyes (P = 0.002, Wilcoxon signed-rank test) and better eyes (P = 0.028). The mean automated visual field (AVF) mean deviation (MD) of available AVFs before shunt was 223.36 dB (range, 233.38 to 27.01 dB) for the worse eye (n = 11) and 219.66 dB (230.11 to 25.91 dB) for the better eye (n = 11). Mean AVF MD deviation of available AVFs after shunt was 220.68 dB (232.13 to 23.97 dB) for the worse eye (n = 11) and 216.35 dB (232.13 to 21.00 dB) for the better eye (n = 11): this improvement was not significant (P = 0.27, P = 0.26, respectively). Independent masked record reviews by 3 neuro-ophthalmologists showed that 9 (53%) patients improved, 5 (29%) unchanged, 1 (6%) worsened, and 2 (12%) were indeterminate. Kaplan-Meier analysis showed a persistent steady decrease of functioning VP shunts over the entire period of 36 months with 80%, 65%, and 48% of VP shunts functioning without replacement, removal, or revision at 12, 24, and 36 months, respectively. CONCLUSION: VP shunts improve or stabilize most IIH patients presenting with severe progressive visual loss or those with visual loss refractive to medical treatment and ONSF. Survival analysis shows persistent decrease of functioning shunts over time.

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

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 <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed. RESULTS: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40). CONCLUSIONS: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

Referral for Ophthalmology Evaluation and Visual Sequelae in Children With Primary Brain Tumors.

Importance: Visual impairment in children with brain tumors has received limited attention, as most pediatric neuro-oncology clinical trials neither require ophthalmologic evaluation on enrollment nor monitor effects of treatment on visual function during and after treatment. Objective: To investigate ophthalmology referral patterns for children with primary brain tumors, the prevalence of visual sequelae, and the association between tumor characteristics and vision-related diagnoses. Design, Setting, and Participants: This retrospective cohort study included 141 children with primary brain tumors treated at Loma Linda University Children's Hospital and Eye Institute, a university-based tertiary referral center, between January 2013 and September 2017. Data analysis was completed in March 2019. Intervention: Comprehensive ophthalmologic evaluation for children with primary brain tumors. Main Outcomes and Measures: Percentage of patients with ophthalmology evaluation, prevalence of abnormal ophthalmic findings, and their association with tumor characteristics. Results: A total of 141 children (73 [52%] male; median [range] age, 7 [0-18] years) with primary brain tumors were enrolled in this study. Seventy-three patients (41 [52%] male; median [range] age, 8 [0-17] years) never had formal ophthalmologic evaluation. Sixty-eight patients (32 [48%] male; median [range] age, 7 [0-18] years) were evaluated by 1 of 4 board-certified, fellowship-trained pediatric and/or neuro-ophthalmologists for any visual impairment over a total of 222 visits. Five-year overall survival for patients who had eye examination was not significantly different from those who did not (mean [SD] survival, 78.3% [6.2%] vs 84.9% [4.7%]). Median (range) time from tumor diagnosis to initial ophthalmologic evaluation was 9 (0-94) months. Only 10 of 68 children (15%) presented with visual symptoms at tumor diagnosis, while 61 of 68 (90%) had abnormal findings on examination, including strabismus (41 [60%]), visual acuity impairment (37 [54%]), amblyopia (26 [38%]), papilledema (24 [35%]), visual field defects (13 [19%]), optic atrophy (12 [18%]), and keratopathy (10 [15%]). Strabismus occurred more frequently in patients with posterior fossa tumors (26 of 68 in posterior fossa vs 15 of 68 in other locations; P = .02). The presence of visual field defects in patients with no visual symptoms was 15% (9 of 58). Radiation was significantly associated with amblyopia (odds ratio, 4.5; 95% CI, 1.2-15.7; P = .02). Conclusions and Relevance: In this study, more than 50% of children with primary brain tumors were not referred for ophthalmologic evaluation. Although visual symptoms were uncommon, visual impairments occurred more frequently than previously reported. Ophthalmologic evaluation is recommended to identify and manage visual impairment and prevent permanent vision loss in children with brain tumors.

Primary peripheral retinal nonperfusion in a family with Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder associated with aggressive arterial aneurysms; rarely, it can have clinical features similar to those of Marfan syndrome, with retinal detachment, myopia, and ectopia lentis. A 19-month-old boy with history of LDS was found to have peripheral retinal nonperfusion in both eyes and a combined traction and exudative retinal detachment of the left eye. Ocular findings in the father, who also had LDS, were normal, but the patient's 34-month-old sister with LDS was also found to have less extensive peripheral retinal nonperfusion. To our knowledge, this is the first report of LDS associated with peripheral retinal nonperfusion in siblings with the same LDS mutation.

Inadvertent intrastromal injection of ophthalmic viscoelastic.

Viscoelastic is an ophthalmic viscosurgical device used to protect ocular tissue and maintain intraocular space during surgical procedures such as cataract removal. To date, the only cases published regarding inadvertent viscosurgical device injection have caused Descemet's membrane detachments. We report the case of a 4-year-old girl who underwent complicated lensectomy with prior history of uveitis and posterior synechia in which intrastromal ophthalmic viscoelastic was inadvertently injected into the stroma, leaving an off-centered opacity. At the time of surgery, no Descemet's membrane detachment was seen. The lensectomy and planned anterior vitrectomy were performed without complication and visual acuity has improved from 20/200 preoperatively to 20/70 at 3 months' follow-up. The corneal opacity resolved within 1 week of surgery, with no evidence of residual visual impairment.