Building and maintaining interprofessional collaborative practice in eyecare: Learnings from the Queensland Paediatric Optometry Alignment Program.

PURPOSE: The Queensland Children's Hospital Paediatric Optometry Alignment Program commenced with a pilot phase to assess its feasibility, effectiveness and acceptability. This study identified the barriers that hinder effective interprofessional collaboration and the facilitators that contribute to its success, and assessed changes in optometrists' satisfaction since the pilot phase of the collaborative care programme. METHODS: Qualitative deductive and inductive content analysis was applied to open-ended free-text survey responses collected in 2018 from the optometrists involved in the Program's pilot phase. The responses were coded using the Theoretical Domains Framework (TDF) to categorise barriers and facilitators into key themes. Key behavioural determinants were mapped to the COM-B (Capability, Opportunity, Motivation-Behaviour) elements of the Behaviour Change Wheel model to identify intervention strategies. Intervention recommendations were derived from behaviour change mapping and compared with programme quality improvement initiatives. A cross-sectional explanatory survey informed by the TDF was conducted within the current 2023 cohort, and a longitudinal comparative analysis was carried out using data from the 2018 survey. RESULTS: Among the 97 surveys distributed in 2018, 44 respondents participated; from this group, 38 individuals contributed a total of 200 free-text responses. Facilitators (240 comments) outnumbered barriers (65 comments). Key facilitators were accessible and timely care, professional development, confidence and positive outcome beliefs. Barriers included communication, information handover, credibility, relationships and skill gaps. Optometrists actively engaged in the programme in 2023 reported heightened satisfaction with their involvement, increased confidence and greater engagement in paediatric eyecare delivery. However, challenges in clinical information transfer persist. CONCLUSION: The interprofessional collaborative model of paediatric eyecare has contributed efficiencies within the health system by building paediatric care capacity in the community, fostering professional credibility and promoting interdisciplinary trust. Insights gained should prove valuable for other paediatric eyecare services exploring hospital-to-community care models.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

BACKGROUND/AIMS: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes. METHODS: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice. RESULTS: For babies receiving ROP treatment, we recommend patient demographics, systemic comorbidities, ROP status, treatment details, ophthalmic and systemic complications of treatment, ophthalmic and neurodevelopmental outcomes at initial treatment, any episodes of retreatment and follow-up examinations in the short and long-term to be collected for use in ROP studies, registries and routine clinical practice. CONCLUSIONS: We recommend these parameters to be used in registries and future studies of ROP treatment, to reduce the variation seen in previous reports and allow meaningful assessments and comparisons. They form the basis of the EU-ROP and the Fight Childhood Blindness! ROP Registries.

The paediatric optometry alignment program - a model of interprofessional collaborative eyecare.

CLINICAL RELEVANCE: Collaboration  between hospital-based ophthalmology and community-based optometry could pave the way to improve access to paediatric eyecare services. BACKGROUND: The Paediatric Optometry Alignment Program (POAP) began in 2016 as a proof-of-concept pilot project that aimed to improve access to specialist paediatric ophthalmology services. If found to be effective at improving patient access, and the quality of care acceptable to patients and professionals then the strategic intent was to upscale the programme to  serve as a model for paediatric eye care in the community. METHODS: Temporal observational trend analysis was used to review ophthalmology clinic appointment waitlists prior and post POAP pilot project commencement. Family satisfaction with post-discharge care was surveyed in a purposive sample of 30 patients.  Aligned optometrists in the program pilot (n = 97) were invited to complete an online survey (response rate 46%; n = 45). RESULTS: The percentage of children waiting longer than clinically recommended fell from 72% to 36%. Sixty-seven percent  of surveyed families had attended a community optometrist as recommended, and all rated the optometry experience from good to excellent.  Participating optometrists reported high levels of satisfaction with involvement in the program, and increased confidence and involvement in paediatric eye care delivery. The need to improve formal transfer  of clinical information was identified. CONCLUSION: Facilitated integrated care between community-based optometrists and a hospital-based ophthalmology department can improve access for tertiary care services, with high satisfaction for families and participating community-based optometrists.

Trampoline Use and Retinal Detachment in Stickler Syndrome.

Stickler syndrome is one of the most common inherited causes of retinal detachment in childhood. We present the case of a 6-year-old boy with Stickler syndrome who developed a retinal detachment in his better seeing eye after prolonged trampoline use. We suggest that trampolining should be avoided in all patients at increased risk of retinal detachment, especially in Stickler syndrome, and in those with other risk factors including high myopia and previous retinal detachments.

Evaluation of virtual accreditation of medical specialist training sites for ophthalmology in Australia and New Zealand during the COVID-19 pandemic.

Objective To evaluate the suitability and acceptability of virtual training post accreditation visits conducted online for medical specialist training in ophthalmology in Australia and New Zealand. Methods A two-phase study (pilot and implementation) was conducted. In the pilot phase, an open-ended observation proforma was used by the authors to independently record their observations, which were later compared and discussed until consensus was achieved. All participants were asked to complete an online survey. A document analysis of accreditation documents was conducted. Observation data were broken down into themes and triangulated with online survey and document analysis results. In the implementation phase, the inspections were observed by one of the authors (SK) and the observation notes were discussed with other authors to obtain a contextual and consensual view. A document analysis of all accreditation-related documentation was undertaken. The documents included in the document analysis were planning and scheduling records, interview and inspection notes, training post inspection fact and document notices and accreditation reports. Finally, a post-inspection focus group of all inspectors was conducted. Results The accreditation interviews adequately addressed all relevant issues with high levels of robustness and reliability. Participants found it more difficult to discuss complex issues virtually compared with onsite visits. The virtual accreditation reports were not any different to what would be expected if a face-to-face accreditation visit had been conducted; however, it was not possible using the virtual inspection to determine the appropriateness of facilities and clinic layout to support and facilitate trainee learning and supervision. Conclusions Virtual accreditation of training posts in medical specialist training is viable in limited circumstances where there are no known complex training post-related issues and the site has not made substantial changes to clinic and theatre layout, equipment and facilities since the previous accreditation.

Community based vision screening in preschool children; performance of the Spot Vision Screener and optotype testing.

BACKGROUND: Children's vision screening children commonly uses optotype-based visual acuity or instrument-based methods measuring amblyogenic risk factors (ARFs). OBJECTIVE: To compare the performance of the Spot Vision Screener (SVS) (PediaVision, Welch Allyn, NY) and a nurse-administered visual acuity screen (NVAS) in identifying ARFs and decreased visual acuity. METHODS: A prospective, cross-sectional population-based study of preschool children in South-East Queensland, Australia. Eligible participants had both forms of screening by trained community nurses. All children with an abnormal result by either method as well as a cohort of randomly selected children who passed both assessments were assessed at a tertiary paediatric ophthalmology clinic. RESULTS: Over a 10 month period, 2237 children (mean age; 64.4 ± 4.0 months) were screened from 38 schools. 6.4% of children failed SVS and 8.3% failed NVAS (with 3.8% overlap, failing both). The positive predictive value (PPV) in identifying either ARFs and/or reduced VA for the SVS and NVAS was 70.4% (95% Confidence Interval (CI): 61.6%-78.2%) and 60.5% (95% CI: 52.6%-67.9%) respectively. Highest PPV to detect either ARFs and/or reduced VA was achieved by a 'hybrid' method by combining failed NVAS and failed SVS: 91.0% (95% CI: 82.4 to 96.3) but this would risk children with sight impairment being missed in the community. CONCLUSION: To our knowledge, this is the first population-based study providing detailed comparative measures of diagnostic accuracy for NVAS and SVS in preschool children. One in ten preschool children failed one or both screens. A number of children who required ophthalmic intervention were missed if only one screening method was utilized.

Clinimetric properties of visuo-perceptual and visuo-cognitive assessment tools used for children with cerebral visual impairment and cerebral palsy or developmental delay: a systematic review.

PURPOSE: The aim of this systematic review is to evaluate the psychometrics and clinical utility of visuo-perceptual and visuo-cognitive assessment tools in children with cerebral visual impairment (CVI) and cerebral palsy (CP) or neurodevelopmental delay (DD). MATERIALS AND METHODS: Five databases (PubMed, EMBASE, SCOPUS, CINAHL, and Cochrane Database) were comprehensively searched from 1970 till June 2021. The PRISMA checklist was utilised to report on the process of selecting eligible papers. The methodological quality of included studies was evaluated using COnsenus-based Standards for the selection of health Measurement INstrument (COSMIN) checklist. RESULTS: Of the 26 assessment tools identified, only seven tools had psychometric evidence supporting their use. Based on COSMIN guidelines, 60% of included studies were rated as inadequate or doubtful for their methodological quality of measurement properties, with equal number being rated as indeterminate on the overall rating. CONCLUSIONS: Cerebral visual impairment due to its varied clinical presentation is often missed in children with CP and DD. There is a paucity of studies reporting on the validity and reliability of functional vision tools. Further studies are needed to conduct high-quality psychometric reporting using the updated COSMIN guidelines to identify appropriate functional vision tools for children with CP or DD.Implications for rehabilitationThere are paucity of studies evaluating the validity and reliability of existing perceptual and cognitive assessment tools in children with cerebral visual impairment (CVI) and cerebral palsy (CP).Development of age-appropriate assessment tools evaluating all aspects of functional vision will assist in providing more holistic child-centric rehabilitation programs.A combination of detailed perinatal history, direct observation, and clinical assessments of functional vision are important to recognise CVI in children with CP.

Amniotic Membrane-Covered Conformer and Fibrin Glue for Toxic Epidermal Necrolysis.

PURPOSE: Stevens-Johnson syndrome and its more severe form, toxic epidermal necrolysis, are immunologic disorders that cause widespread blistering of the skin and mucous membranes. Its incidence is higher in children and can lead to long-term disabling ocular surface complications that can be averted with amniotic membrane transplantation early in the disease. To introduce an amniotic membrane treatment technique that is time efficient and minimally invasive but still allows for extensive coverage of the ocular mucosal surfaces to prevent and lessen the severity of the complications from ocular surface sequelae. METHODS: The procedure was undertaken in the operating room under general anesthesia. Symblephara were divided before an amniotic membrane-covered conformer was placed into the fornices. Fibrin glue was used to secure the conformer and to keep the palpebral aperture closed. Topical chloramphenicol 0.5% and prednisolone 0.5% were prescribed 4 times a day. RESULTS: After 7 days, the conformers were removed and new amniotic membrane-covered conformers were reapplied in both eyes for a further week. After the second round of treatment, the conformers were left out for 3 days. Inferior symblephara reformed in the left lower fornix, and therefore, a third round of treatment was undertaken in the left eye only, which was then removed after 7 days. A follow-up at 8 weeks revealed 20/20 vision with minimal symblephara in either eye. CONCLUSIONS: This novel technique, using an amniotic membrane-covered conformer in combination with fibrin glue, allows for the coverage of the entire ocular surface and protection of the lid margins while requiring minimal preparation and surgical time. This technique could also be used in patients with other cicatrizing ocular surface conditions, such as chemical or thermal injuries or postreconstructive surgery of the fornices.

Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry.

PURPOSE: To report the relative frequencies of childhood and early onset glaucoma subtypes and their genetic findings in a large single cohort. DESIGN: Retrospective clinical and molecular study. PARTICIPANTS: All individuals with childhood glaucoma (diagnosed 0 to <18 years) and early onset glaucoma (diagnosed 18 to <40 years) referred to a national disease registry. METHODS: We retrospectively reviewed the referrals of all individuals with glaucoma diagnosed at <40 years of age recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Subtypes of glaucoma were determined using the Childhood Glaucoma Research Network (CGRN) classification system. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma. MAIN OUTCOME MEASURES: The phenotype and genotype distribution of glaucoma diagnosed at <40 years of age. RESULTS: A total of 290 individuals (533 eyes) with childhood glaucoma and 370 individuals (686 eyes) with early onset glaucoma were referred to the ANZRAG. Primary glaucoma was the most prevalent condition in both cohorts. In the childhood cohort, 57.6% of individuals (167/290, 303 eyes) had primary congenital glaucoma (PCG), and 19.3% (56/290, 109 eyes) had juvenile open-angle glaucoma. Juvenile open-angle glaucoma constituted 73.2% of the early onset glaucoma cohort (271/370, 513 eyes). Genetic testing in probands resulted in a diagnostic yield of 24.7% (125/506) and a reclassification of glaucoma subtype in 10.4% of probands (13/125). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with nonacquired ocular anomalies (56.5%). Biallelic variants in CYP1B1 (n = 29, 23.2%) and heterozygous variants in MYOC (n = 24, 19.2%) and FOXC1 (n = 21, 16.8%) were most commonly reported among probands with a molecular diagnosis. Biallelic CYP1B1 variants were reported in twice as many female individuals as male individuals with PCG (66.7% vs. 33.3%, P = 0.02). CONCLUSIONS: We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification. Primary glaucoma was most prevalent. Genetic diagnoses ascertained in 24.7% of probands supported clinical diagnoses and genetic counseling. International collaborative efforts are required to identify further genes because the majority of individuals still lack a clear molecular diagnosis.

Acute red eye in children: A practical approach.

BACKGROUND: Acute red eye in a child is a common ocular presentation in general practice. It can arise from a wide spectrum of pathologies and involve various ocular structures. OBJECTIVE: The aim of this article is to provide a framework for the general practitioner to assess and manage a child presenting with a red eye, with a focus on cases that require immediate referral. DISCUSSION: Most paediatric red eyes are benign and can be safely managed in general practice. However, this requires thorough history-taking and examination together with the ruling out of red flags. Assessment of a child with a red eye may pose specific challenges that can usually be overcome by focused history-taking and opportunistic examination. Urgent referral for examination under sedation or anaesthesia is indicated when there is suspicion of a vision-threatening cause and/or assessment in the clinic is unsuccessful.

Epidemiology of severe ocular trauma following the implementation of alcohol restrictions in Far North Queensland.

IMPORTANCE: Indigenous communities of Far North Queensland (FNQ) have one of the highest incidences of alcohol-related ocular trauma globally. BACKGROUND: To review the epidemiology of closed- and open-globe trauma admitted to Cairns Hospital from FNQ health districts following the implementation of alcohol restrictions in Indigenous communities. DESIGN: Retrospective study of cases from January 2014 to December 2018. PARTICIPANTS: A total of 142 cases identified from ICD-10 clinical-coding data. METHODS: Records were reviewed to determine demographics, clinical details and outcomes. MAIN OUTCOME MEASURES: Annual incidence by demography and ethnicity (Indigenous vs non-indigenous). RESULTS: Estimated annual incidence was 10.4/100 000 population (open-globe: 3.6/100 000, closed-globe: 6.8/100 000 population). Incidence rate ratio was 2.8× higher in Indigenous (22.8/100 000 population) compared to non-indigenous populations. Injury from assault was 8.2× higher in the Indigenous population. Alcohol was involved in 76% of assaults. Paediatric injuries comprised 20.4% of the cohort, with Indigenous children over-represented (44.8% of children). Visual acuity (VA) at presentation ranged from -0.08 logMAR to no-perception of light (NPL), with 41.8% poorer than +1.00 logMAR. Final VA ranged from -0.18 logMAR to NPL. Mean final VA was significantly better for closed- than open-globe injuries (+0.43 vs +1.01 logMAR). Ruptures had the poorest outcomes (mean +1.65 logMAR). CONCLUSIONS AND RELEVANCE: The overall incidence of severe ocular trauma in FNQ has decreased compared to that reported from 1995 to 2002. The extremely high incidence observed in the Indigenous communities of Cape York has decreased dramatically since the introduction of Alcohol Management Plans. Nevertheless, the Indigenous population still experiences significantly higher rates of severe ocular trauma, particularly from assault.

Relationship between brain structure and Cerebral Visual Impairment in children with Cerebral Palsy: A systematic review.

BACKGROUND: Cerebral Visual Impairment (CVI) is very common yet often unrecognised visual dysfunction in children with Cerebral Palsy (CP). Magnetic Resonance Imaging (MRI) is the diagnostic tool in the investigation of brain lesions in children with CP and CVI. AIM: The aim of this systematic review is to evaluate the relationship between brain structure and CVI, as determined by MRI in children with CP. METHODS AND PROCEDURES: A comprehensive search of 5 database (PubMed, EMBASE, SCOPUS, CINAHL and Cochrane Database) was undertaken up until June 2019. The PRISMA checklist was then utilised to report on the process of selecting eligible papers. A total of 30 observational studies met the full inclusion criteria. Further, STROBE checklist was employed to report on the observational studies. OUTCOMES AND RESULTS: Periventricular leucomalacia on MRI was found to have a strong association with CVI in all 30 studies. Only 13 (43 %) studies described dorsal and/ ventral stream dysfunction. There was ambiguity in the definition of CVI. CONCLUSIONS AND IMPLICATIONS: The overall level of evidence correlating different patterns of CVI and CP (based on GMFCS, motor type and distribution) and MRI was low. Further studies utilising advances in MRI are needed to understand brain reorganisation and patterns of CVI and suggest rehabilitation therapy inclusive of vision.

Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review.

Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction. Ophthalmic manifestations are present in 60% of these CDG. The ophthalmic manifestations in N-glycosylation-deficient patients have been described elsewhere. The present review documents the spectrum and incidence of eye disorders in patients with pure O-glycosylation defects with the aim of assisting diagnosis and management and promoting research.

Models of care in tele-ophthalmology: A scoping review.

The objective of this review was to identify and describe telehealth models of care for ophthalmic services. We conducted a scoping review of the literature to identify how ophthalmic care can be delivered by telehealth. We searched the PubMed database to identify relevant articles which were screened based on pre-defined inclusion criteria. For included articles, data were extracted, categorised and analysed. Synthesis of findings was performed narratively. The scoping review included 78 articles describing 62 discrete tele-ophthalmic models of care. Tele-ophthalmic models of care can be used for consultative service, screening, triage and remote supervision. The majority of services were for general eye care and triage ( n = 17; 26%) or emergency services ( n = 8; 12%). The most common conditions for disease-specific models of care were diabetic retinopathy ( n = 14; 21%), and glaucoma ( n = 8; 12%). Most models of care involved local clinicians capturing images and transmitting them to an ophthalmologist for assessment. This scoping review demonstrated tele-ophthalmology to be feasible for consultation, screening, triage and remote supervision applications across a broad range of ophthalmic conditions. A large number of models of care have been identified and described in this review. Considerable collaboration between patient-end clinicians and substantial infrastructure is typically required for tele-ophthalmology.

Retinopathy of prematurity: the high cost of screening regional and remote infants.

IMPORTANCE: Demand for retinopathy of prematurity (ROP) screening is increasing for infants born at rural and regional hospitals where the service is not generally available. The health system cost for screening regional/remote infants has not been reported. BACKGROUND: The objective of this study is to evaluate the cost of ROP screening at a large centralized tertiary neonatal service for infants from regional/rural hospitals. DESIGN: This is a retrospective study to establish the cost of transferring regional/rural infants to the Royal Brisbane and Women's Hospital for ROP screening over a 28-month period. PARTICIPANTS: A total of 131 infants were included in this study. METHODS: Individual infant costs were calculated from analysis of clinical and administrative records. MAIN OUTCOME MEASURES: Economic cost of ROP screening for all transfers from regional/rural hospitals to Royal Brisbane and Women's Hospital. RESULTS: The average economic cost of ROP screening for this cohort was AUD$5110 per infant screened and the total cost was AUD$669 413. The average cost per infant screened was highest for infants from a regional centre with a population of 75 000 (AUD$14 856 per child), which was also geographically furthest from Brisbane. No infant in this cohort transferred from a regional nursery reached criteria for intervention for ROP by standard guidelines. CONCLUSIONS AND RELEVANCE: Health system costs for ROP screening of remote infants at a centralized hospital are high. Alternative strategies using telemedicine can now be compared with centralized screening.

Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective.

The population of infants at risk for retinopathy of prematurity (ROP) varies by world region; in countries with well developed neonatal intensive care services, the highest risk infants are those born at less than 28 weeks gestational age (GA) and less than 1 kg at birth, while, in regions where many aspects of neonatal intensive and ophthalmological care are not routinely available, more mature infants up to 2000 g at birth and 37 weeks GA are also at risk for severe ROP. Treatment options for both groups of patients include standard retinal laser photocoagulation or, more recently, intravitreal anti-VEGF drugs. In addition to detection and treatment of ROP, this review highlights new opportunities created by telemedicine, where screening and diagnosis of ROP in remote locations can be undertaken by non-ophthalmologists using digital fundus cameras. The ophthalmological care of the ROP infant is undertaken in the wider context of neonatal care and general wellbeing of the infant. Because of this context, this review takes a multi-disciplinary perspective with contributions from retinal vascular biologists, pediatric ophthalmologists, an epidemiologist and a neonatologist. This review highlights the latest insights regarding cellular and molecular mechanisms in the formation of the retinal vasculature in the human infant, pathogenesis of ROP, detection and treatment of severe ROP, the risks and benefits of anti-VEGF therapy, the identification of new therapies over the horizon, and the optimal neonatal care regimen for best ROP outcomes, and the benefits and pitfalls of telemedicine in the remote screening and diagnosis of ROP, all of which have the potential to improve ROP outcomes.

Validity of ophthalmology surgical competency assessment rubric for strabismus surgery in resident training.

The Accreditation Council for Graduate Medical Education (ACGME) requires US residency programs to assess ophthalmology residents for competency in 6 core areas. Ophthalmic surgical skills are currently part of the ACGME "Patient Care" competency, although some have advocated for a seventh competency, "Surgical Skills." The Ophthalmology Surgical Competency Assessment Rubric for Strabismus Surgery in Resident Training ( OSCAR: Strabismus) tool was designed to aid in the assessment of surgical skills using procedure specific behavioral anchors. The present study evaluated inter-rater agreement of the OSCAR: Strabismus tool in the assessment of resident performance. OSCAR: Strabismus evaluations of resident surgical strabismus cases were performed by a multinational group of faculty strabismus surgeons. Cronbach α statistical analysis of the completed evaluations revealed high inter-rater agreement, indicating the OSCAR: Strabismus is a reliable tool to facilitate assessment of resident strabismus surgical skills.

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants.

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants.

Nitroxides have been exploited as profluorescent probes for the detection of oxidative stress. In addition, they deliver potent antioxidant action and attenuate reactive oxygen species (ROS) in various models of oxidative stress, with these results ascribed to superoxide dismutase or redox and radical-scavenging actions. Our laboratory has developed a range of novel, biostable, isoindoline nitroxide-based antioxidants, DCTEIO and CTMIO. In this study we compared the efficiency of these novel compounds as antioxidant therapies in reducing ROS both in vivo (rat model) and in vitro (661W photoreceptor cells), with the established antioxidant resveratrol. By assessing changes in fluorescence intensity of a unique redox-responsive probe in the rat retina in vivo, we evaluated the ability of antioxidant therapy to (1) ameliorate ROS production and (2) reverse the accumulation of ROS after complete, acute ischemia followed by reperfusion (I/R). I/R injury induced a marked decrease in fluorescence intensity over 60 min of reperfusion, which was successfully ameliorated with each of the antioxidants. DCTEIO and CTMIO reversed the accumulation of ROS when administered intraocularly post ischemic insult, whereas, the effect of resveratrol was not significant. We also investigated our novel agents' capacity to prevent ROS-mediated metabolic dysfunction in the 661W photoreceptor cell line. Cellular stress induced by the oxidant, tert-butyl hydroperoxide, resulted in a loss of spare mitochondrial respiratory capacity (SMRC) and in the extracellular acidification rate in 661W cells. DCTEIO antioxidant administration successfully reduced the loss of SMRC. Together, these findings show we can quantify dynamic changes in cellular oxidative status in vivo and suggest that nitroxide-based antioxidants may provide greater protection against oxidative stress than the current state-of-the-art antioxidant treatments for ROS-mediated diseases.