Does general anesthesia or intravitreal injection affect neurodevelopment in children undergoing ophthalmic procedures?

PURPOSE OF REVIEW: To review recent studies on potential neurodevelopmental impacts on the pediatric population through general anesthesia events or intravitreal anti-vascular endothelial growth factor (VEGF) injection. RECENT FINDINGS: Studies on this topic have been extensive with varied reported neurodevelopmental outcomes. Initial investigations in rodents and primates showed negative impact of anesthetics on neurodevelopment. Subsequent retrospective human reviews had mixed results whereas more recent sibling and prospective studies have been published without evidence of clinically significant impact. A similar narrative has more recently come to play regarding the long-term effects of intravitreal injections used in neonates with retinopathy of prematurity. Publications initially indicated a negative correlation whereas later reviews have found no difference between those receiving injections versus laser treatment. SUMMARY: Given that recent data on both general anesthesia events and intravitreal anti-VEGF injections do not show a long-term negative neurodevelopmental impact, ocular procedures needed to improve a pediatric patient's vision or quality of life should not be delayed.

Ophthalmia neonatorum treatment and prophylaxis: IPOSC global study.

INTRODUCTION: Characteristics of ophthalmia neonatorum (ON) amongst paediatric ophthalmologists remain unclear. The purpose of this current study is to examine the incidence, diagnosis, treatment, and prophylaxis of ON cases presenting to members of the American Association of Paediatric Ophthalmology and Strabismus (AAPOS). METHODS: An email containing a web link to a survey was sent to all members of AAPOS. The questionnaire examined the incidence of ON, etiology, diagnostic methods, treatment, and prophylaxis of the disease in different countries around the world. RESULTS: Two hundred and ninety-one ophthalmologists answered the questionnaire. Most were from North America (52.94 %). One hundred and seventy-six (60.69 %) ophthalmologists encountered 0-5 cases of ON per year. The most common pathogens causing ON was Chlamydia trachomatis (35.37 %). Two hundred and forty-two (85.21 %) treat empirically when encountering ON during the first 10 days of life and 205 (75.09 %) after the first 10 days of life. In both cases, erythromycin was the most common first line of treatment. Two hundred and twenty-two (78.72 %) ophthalmologists replied that prophylactic treatment is required in their country. The most common agent for prophylaxis was erythromycin ointment (71.50 %). CONCLUSIONS: We found that the incidence of ON per year per practitioner is 0-5 cases, the most common etiology is C. trachomatis, and most infants receive prophylaxis and treatment.

Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).

Blindness Secondary to Retinopathy of Prematurity in Sub-Saharan Africa.

PURPOSE: Retinopathy of Prematurity (ROP) has been suggested to be increasing in Africa. However, it was only previously documented as a cause of blindness in 8 of 48 (16.7%) sub-Saharan African countries. The purpose of this study was to better understand the magnitude and breadth of blindness from ROP in sub-Saharan Africa. METHODS: A questionnaire was sent to 455 ophthalmologists practicing in sub-Saharan Africa; the questionnaire was available in English, French and Portuguese. RESULTS: Responses were received from 132 of 455 (29%) ophthalmologists to whom the survey was sent. Eighty-three respondents were identified as ROP-involved ophthalmologists and were from 26 of 48 (54%) sub-Saharan African countries. Ophthalmologists in 23 countries reported that they examined at least one child who was blind from ROP during the last 5 years. Sixteen of these countries had not previously reported cases of blindness from ROP in the literature. The perceived occurrence of Type 1 or more severe ROP was reported to be increasing by 31 of 77 (40%) ROP-involved ophthalmologists. ROP-involved pediatric ophthalmologists and retinal surgeons reported the number of infants they examined annually with Type 1 or more severe ROP increased from a median of 1 (range: 0-15) to a median of 4 (range: 0-40) from 2015 to 2019. ROP was estimated to be the cause of blindness for 10% of all blind children examined by ROP-involved pediatric ophthalmologists and retinal surgeons during 2019. CONCLUSIONS: ROP is becoming a more important and widespread cause of childhood blindness in sub-Saharan Africa.

Monitoring the conjunctiva for carbon dioxide and oxygen tensions and pH during cardiopulmonary bypass.

The purpose of this study was to measure, for the first time, multiple physiologic parameters of perfusion (pH, PCO2, PO2, and temperature) from the conjunctiva of adult patients during cardiopulmonary bypass while undergoing cardiothoracic surgery. Ten patients who underwent either intracardiac valve repair, atrial septal defect repair, or coronary artery bypass graft surgery had placement of a sensor which directly measured pH, PCO2, PO2, and temperature from the conjunctiva. Data were stratified into seven phases (0-5 minutes prior to bypass; 0-5, 6-10, and 11-15 minutes after initiation of bypass; 0-5 minutes prior to conclusion of bypass; and 0-5 and 6-10 minutes after bypass) and analyzed using a mixed model analysis.The change in conjunctival pH over the course of measurement was not statistically significant (p = .56). The PCO2 level followed a quadratic pattern, decreasing from a mean pre-bypass level of 37.7 mmHg at baseline prior to the initiation of cardiopulmonary bypass to a nadir of 33.2 mmHg, then increasing to a high of 39.4 mmHg at 6-10 minutes post bypass (p < .01). The PO2 declined from a mean pre-bypass level of 79.5 mmHg to 31.3 mmHg by 6-10 minutes post bypass and even post-bypass, it never returned to baseline values (p < .01). Temperature followed a pattern similar to PCO2 by returning to baseline levels as the patient was re-warmed following bypass (p < .01). There was no evidence of any eye injury or inflammation following the removal of the sensor. In the subjects studied, the conjunctival sensor yielded reproducible measurements during the various phases of cardiopulmonary bypass without ocular injury. Further study is necessary to determine the role of conjunctival measurements in critical settings.

Oxygen management among infants in neonatal units in sub-Saharan Africa: a cross-sectional survey.

OBJECTIVES: To provide more comprehensive data on the management of oxygen supplementation in neonates in sub-Saharan Africa. STUDY DESIGN: An online survey on the management of oxygen supplementation for infants in neonatal units was sent to 278 healthcare personnel in sub-Saharan Africa. RESULTS: One hundred and nine responses from 82 neonatal care units in 54% (26/48) sub-Saharan African countries were received. All units had the capacity to provide oxygen supplementation. However, only 50% (38/76) had access to blend oxygen with medical air and 1% (1/75) had the capacity to blend oxygen/air for every infant. Although 96% (72/75) of units could monitor oxygen saturation, monitoring was mostly intermittent and only 32% (24/75) were able to monitor oxygen saturation in every infant receiving oxygen supplementation. CONCLUSIONS: Findings indicate that oxygen supplementation is inadequately managed in neonatal units in sub-Saharan Africa, which may put infants at risk of developing severe ROP.

Current management of retinopathy of prematurity in sub-Saharan Africa.

PURPOSE: To survey current oxygen management, screening criteria, and methods for treating retinopathy of prematurity (ROP) in sub-Saharan Africa. METHODS: An online survey was sent to ophthalmologists and neonatologists practicing in sub-Saharan Africa. RESULTS: Ophthalmologists and neonatologists from 15 of 49 countries (31%) in sub-Saharan Africa responded. Neonatologists reported treating a median of 15 infants with supplemental oxygen per week but only had a median of 3.5 oxygen-measuring devices and a median of zero oxygen blenders in their units. Ophthalmologists reported screening a median of 5 infants per week for ROP and treating 2 infants each month for ROP. Most ophthalmologists (24/27 [89%]) had access to anti-vascular endothelial growth factor drugs to treat ROP, but only 13 of 27 (48%) had access to a laser. CONCLUSIONS: Survey results reveal an urgent need for additional oxygen- management equipment in hospitals in sub-Saharan Africa.

Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus.

BACKGROUND: The purpose of this study was to report the effect of combining the Kestenbaum procedure with posterior fixation suture for infantile horizontal nystagmus with anomalous head posture (AHP) in children. METHODS: Nine consecutive patients who underwent combined Kestenbaum procedure plus posterior fixation suture to the recessed muscles at the same time were retrospectively studied. All patients were orthotropic before surgery and were followed for at least 6 months. Pre- and postoperative AHP and binocular corrected visual acuity (BCVA), and ocular alignment were assessed. RESULTS: Mean age at surgery was 4.8 +/- 1.5 years. The average follow-up was 29.7 months. The average head turn preoperatively was 27.4 degrees and postoperatively 7.2 degrees . The average net change in AHP was 24.8 degrees (P = 0.008). Seven of 9 patients (78%) achieved a residual head turn of 10 degrees or less. The average Log Mar BCVA was 0.33 preoperatively and 0.31 postoperatively (P = 0.68). Only 1 patient needed additional surgery for residual horizontal AHP. No patient developed strabismus. CONCLUSION: Combined Kestenbaum procedure with posterior fixation suture was an effective and stable procedure in reducing AHP of the range of 20 degrees to 35 degrees in children with infantile nystagmus.

Decreased Binocular Summation in Strabismic Amblyopes and Effect of Strabismus Surgery.

PURPOSE: Binocular summation (BiS) occurs when binocular visual function surpasses that of the better eye alone. We sought to evaluate whether strabismic amblyopia reduces BiS more than strabismus alone, and determine whether BiS improves in strabismic amblyopes after strabismus surgery. METHODS: We prospectively recruited 15 patients with strabismic amblyopia who then underwent strabismus surgery. Thirty age-matched normal subjects and 30 non-amblyopic strabismic patients served as controls. Subjects underwent binocular and monocular visual acuity testing on high-contrast Early Treatment Diabetic Retinopathy Study (ETDRS) as well as 2.5% and 1.25% Sloan low contrast acuity (LCA) charts. BiS was calculated as the difference between better eye and binocular scores. RESULTS: Strabismic amblyopes and strabismic controls did not significantly differ in preoperative BiS, but both had subnormal BiS preoperatively on LCA charts. Among 11 strabismic amblyopes with preoperative and postoperative BiS measurements, average postoperative BiS was not significantly different from preoperative. Improved LCA BiS postoperatively occurred in some patients and was associated with measurable preoperative stereoacuity (P=0.02), older age at strabismus onset (P=0.02), and larger preoperative angle of strabismus (P=0.0043). CONCLUSIONS: In this preliminary study, strabismic amblyopes experienced subnormal BiS, but amblyopia generally did not further impair BiS beyond that due to strabismus alone. Some strabismic amblyopes experienced improved low-contrast BiS after strabismus surgery. This suggests that further investigation in larger groups of patients should be undertaken to analyze a previously unrecognized functional benefit of strabismus surgery in strabismic amblyopes.

Binocular Summation and Control of Intermittent Exotropia.

BACKGROUND: Binocular summation (BiS), or improvement in binocular vision exceeding the better eye alone, is affected by strabismus. Being easily measured, BiS may be a useful indicator for subjective outcomes like stereopsis in strabismus. This study aims to investigate the relationship between BiS and measures of control of intermittent exotropia (IXT). METHODS: Patients with IXT were recruited before undergoing strabismus surgery and underwent tests of binocular and monocular high- and low-contrast visual acuity, stereopsis at distance and near, and Newcastle Control Score (NCS), a score developed by incorporating home control and clinic control criteria into a control rating scale. BiS was calculated using high-contrast Early Treatment of Diabetic Retinopathy Study (ETDRS) and Sloan low-contrast acuity charts (LCA) at 2.5% and 1.25% contrast as the difference between the binocular score and that of the better eye. The relationship between BiS and measures of IXT control (NCS and distance near stereoacuity disparity) was evaluated using a correlation analysis by Spearman correlation coefficients and the Kruskal-Wallis test. RESULTS: Thirty-four patients were included (mean [± standard deviation (SD)] age 19±16 years) having a mean (±SD) of 26±16Δ IXT at distance and 20±16Δ at near. Mean (±SD) BiS for ETDRS and Sloan LCA at 2.5% and 1.25% was 0.8±3.6, 1.9±6.0, and -2.3±7.2, respectively. The Spearman correlation coefficient of BiS and NCS was -0.53 (95% CI -0.85 to -0.25) for 2.5% LCA and -0.43 (95% CI -0.77 to -0.13) for 1.25% LCA. BiS at 2.5% LCA (P=0.006) and at 1.25% LCA (P=0.029) significantly differed between the groups based on NCS score groupings (1-3, 4-6, and 7-9), with patients who had better control scores having higher levels of BiS. BiS did not differ significantly between patients grouped according to the difference between stereoacuity measured at near versus distance. CONCLUSION: Significantly lower low-contrast BiS in patients with higher NCS may suggest that decreased BiS is associated with less control in IXT. This finding suggests that BiS may reflect control in IXT across a population of patients with IXT.

Necrotizing Tenon's capsule infection in a lymphopenic Down syndrome patient following strabismus surgery.

Periocular infection is a rare complication of strabismus surgery. We describe a case of necrotizing Tenon's capsule infection after uncomplicated strabismus surgery in a boy with Down syndrome and blepharitis. Pathologic diagnosis was severe acute necrotizing inflammation with Gram positive coccal forms. Resolution of infection occurred after surgical debridement and intravenous and topical antibiotics. Work-up revealed lymphopenia related to Down syndrome. Patients with Down syndrome may have risk factors for postoperative infection including blepharitis and immunologic abnormalities.

Prospective, Randomized Clinical Trial of Povidone-Iodine 1.25% Solution Versus Topical Antibiotics for Treatment of Bacterial Keratitis.

PURPOSE: To compare povidone-iodine 1.25% ophthalmic solution with topical antibiotics for treatment of bacterial keratitis in areas of the world where use of effective topical antibiotics may not be an option. STUDY DESIGN: Randomized, controlled, investigator-masked clinical trial. METHODS: We randomized 172 individuals with bacterial keratitis to topical treatment with povidone-iodine or antibiotics (neomycin-polymyxin B-gramicidin in the Philippines; ciprofloxacin 0.3% in India). Using survival analysis, we compared intervals from start of treatment to "presumed cure" (primary outcome measure, defined as a closed epithelial defect without associated inflammatory signs) and to "recovering" (residual epithelial defect <1 mm2 with only minimal inflammation). RESULTS: Median interval to presumed cure in the Philippines was 7 days for povidone-iodine and 7 days for neomycin-polymyxin B-gramicidin (95% confidence interval [CI] for difference in median interval, -9.5 to 0.7 days) and in India was 12 days for povidone-iodine and 17 days for ciprofloxacin (95% CI, -35.2 to 3.2 days). Hazard ratio (HR) for presumed cure among those treated with povidone-iodine (vs antibiotics) was 1.46 in the Philippines (95% CI, 0.90-2.36; P = .13) and 1.70 in India (95% CI, 0.73-3.94; P = .22). Comparisons of intervals to recovering and HR for recovering also revealed no significant differences between treatment groups in either country. CONCLUSIONS: There is no significant difference between the effect of topical povidone-iodine 1.25% and topical antibiotics commonly available in the developing world for treatment of bacterial keratitis. Povidone-iodine 1.25%, which is widely available and inexpensive, can be considered for treatment of bacterial keratitis when antibiotic treatment is not practical.

Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract.

PURPOSE: To further elucidate the cataract phenotype, and identify the gene and mutation for autosomal dominant cataract (ADC) in an American family of European descent (ADC2) by sequencing the major intrinsic protein gene (MIP), a candidate based on linkage to chromosome 12q13. DESIGN: Observational case series and laboratory experimental study. METHODS: We examined two at-risk individuals in ADC2. We PCR-amplified and sequenced all four exons and all intron-exon boundaries of the MIP gene from genomic and cloned DNA in affected members to confirm one variant as the putative mutation. RESULTS: We found a novel single deletion of nucleotide (nt) 3223 (within codon 235) in exon four, causing a frameshift that alters 41 of 45 subsequent amino acids and creates a premature stop codon. CONCLUSIONS: We identified a novel single base pair deletion in the MIP gene and conclude that it is a pathogenic sequence alteration.

Improvement in binocular summation after strabismus surgery.

IMPORTANCE: Binocular summation (BiS), or improvement in visual acuity using binocular vision compared with the better eye alone, is diminished in patients with strabismus. However, it is still not known how strabismus surgery affects BiS. OBJECTIVE: To determine whether BiS improves after strabismus surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 97 patients undergoing strabismus surgery between September 1, 2011, and January 31, 2014, comparing preoperative and postoperative measures of BiS. Patients were recruited within 1 month before undergoing strabismus surgery. The study took place at an academic pediatric ophthalmology and strabismus practice. INTERVENTION: Strabismus surgery. MAIN OUTCOMES AND MEASURES: All patients underwent high- and low-contrast visual acuity testing binocularly and monocularly at preoperative and 2-month postoperative visits. Binocular summation was calculated for high-contrast Early Treatment of Diabetic Retinopathy Study charts and Sloan low-contrast acuity charts at 2.5% and 1.25% contrast as the difference between the binocular score and that of the better eye. Preoperative and postoperative values were compared. RESULTS: There was an improvement in BiS at the 2 low-contrast levels for all patients and for all contrast levels in the 75 patients in whom surgery successfully restored binocular alignment. For low-contrast acuity, the proportion of patients with a BiS score of at least 5 letters postoperatively was almost twice that of preoperatively (21% to 30% and 13% to 26% for 2.5% contrast and 1.25% contrast, respectively). Similarly, the proportion of patients with binocular inhibition (BiS score worse by at least 5 letters than the better eye score) was decreased postoperatively at all contrast levels (from 22% to 14% for 1.25% contrast). Thirty-one percent of patients experienced improvement in BiS scores postoperatively at the lowest contrast level. CONCLUSIONS AND RELEVANCE: Binocular summation scores improved postoperatively in most patients undergoing strabismus surgery. This occurred most frequently at the lowest contrast level. These findings suggest that improved BiS could represent a newly recognized functional benefit from the surgical correction of strabismus. Further studies evaluating the correlation of BiS with stereopsis, visual field expansion, and quality of life will be necessary to fully evaluate the role that improved BiS has in improving binocularity postoperatively.

X-linked Megalocornea Associated with the Novel CHRDL1 Gene Mutation p.(Pro56Leu*8).

BACKGROUND: The genetic basis of X-linked megalocornea (MGC1) was reported in 2012 to be caused by mutations in the CHRDL1 gene. We sought to confirm that mutations in CHRDL1 are associated with MGC1 in a previously unreported pedigree. MATERIALS AND METHODS: Slit lamp examination, corneal pachymetry, corneal topography and DNA collection for screening of the CHRDL1 gene were performed for members of an affected family. RESULTS: Examination of a woman and her four sons, ranging in age between 3 and 15 years, demonstrated horizontal corneal diameters of 14 mm in three of the four sons and a normal corneal diameter of 12 mm in the mother and other son. Central corneal thickness in the individuals with enlarged corneal diameters averaged 474 microns, compared to 604 microns in their unaffected brother. Corneal topographic imaging demonstrated an average K value of 44.4 D in the affected individuals compared with 41.6 D in their unaffected sibling. Screening of the CHRDL1 gene demonstrated the novel hemizygous frameshift mutation c.167delC (p.(Pro56Leu*8)) in exon 3 in the affected individuals and in the heterozygous state in their mother. This mutation was not present in the unaffected brother or in unrelated controls. CONCLUSION: We provide the initial confirmation that X-linked megalocornea is associated with mutations in the CHRDL1 gene.

Quality of life in adults with strabismus.

PURPOSE: To assess relative quality of life in patients with strabismus. DESIGN: Retrospective cohort study. METHODS: The 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was performed in 42 strabismic adults over the age of 50 years at a single institution. Subscale scores were compared with those of patients with other ocular diseases, including diabetic retinopathy, age-related macular degeneration (AMD), glaucoma, cataract, cytomegalovirus (CMV) retinitis, and low vision. RESULTS: Median visual acuity was 20/20 (range 20/12.5-20/50), and 34 patients (81%) reported diplopia. Strabismic patients performed the same or worse on nearly all vision-related subscales than did patients with diabetic retinopathy, age-related macular degeneration, glaucoma, cataract, and CMV retinitis. Additionally, strabismic patients reported significantly worse ocular pain than all comparison groups before any surgery was performed. CONCLUSIONS: Strabismus impacts quality of life through both functional and psychosocial factors. Physicians treating strabismic patients should recognize these quality-of-life issues and address them accordingly.

Corneal topography of neonates and infants.

OBJECTIVE: To evaluate corneal curvature by direct topographic analysis during the first 6 months of life. METHODS: We evaluated corneal topography in 200 infants using a specialized handheld topographic instrument at a mean of 1.6 days after birth, and in some again at 3 and 6 months in the newborn nursery and ophthalmology clinic of a public hospital. RESULTS: At birth, the mean central corneal power measured 48.5 diopters (D) (95% confidence interval [CI], 48.2-48.8 D; range, 41.4-56.0 D) and astigmatism measured 6.0 D (95% CI, 5.6-6.3 D), usually "with the rule" (80%) with a mean axis of 95 degrees . The mean astigmatism on the semimeridian map at 3 mm was 6.4 D (95% CI, 6.0-6.8 D); and at 5 mm, 5.9 D (95% CI, 5.4-6.3 D). At birth, neonates delivered vaginally had a greater frequency of with-the-rule astigmatism than those delivered by cesarean section (P = .02). By 6 months, the mean central corneal power and astigmatism decreased to 43.0 (95% CI, 41.3-43.1) D and 2.3 (95% CI, 1.4-3.2) D, respectively (P<.005 for each). CONCLUSIONS: Newborns have steep, high, astigmatic (generally with-the-rule) corneas at birth that flatten significantly by the age of 6 months. The method of delivery can affect the astigmatic axis at birth.

A controlled trial of povidone-iodine to treat infectious conjunctivitis in children.

PURPOSE: To report the efficacy of povidone-iodine as a treatment for conjunctivitis in pediatric patients. DESIGN: Double-masked, controlled, prospective clinical trial. METHODS: In an ophthalmology clinic in a general hospital in Manila, Philippines, 459 children (mean [SD] age 6.6 [6.6] years; range, 7 months-21 years) with acute conjunctivitis were studied. Infected eyes were cultured for bacteria and underwent immunofluorescent testing for Chlamydia trachomatis. Viral conjunctivitis was diagnosed if bacterial cultures were negative and diagnostic criteria were met. Subjects were alternated to receive povidone-iodine 1.25% or neomycin-polymyxin-B-gramicidin ophthalmic solution, one drop 4 times daily in the affected eye. Ocular inflammation was evaluated daily by the family or patient and weekly by an ophthalmologist. The main outcome measures were days until cured and proportion cured after 1 and 2 weeks of treatment. RESULTS: Despite adequate statistical power (power >80% for a 1-day difference and P <.05), there was no significant difference between treatment groups regarding the number of days to cure or proportion cured at 1 or 2 weeks whether caused by bacteria or virus (P =.133-.824 for the four comparisons). After 1 week of treatment, povidone-iodine cured marginally more chlamydial infections than the antibiotic (P =.057). By 2 weeks, fewer chlamydial infections were cured than those of viral or bacterial etiology (P =.0001). The younger the patient, the faster their conjunctivitis resolved (R = 0.13, P =.013). CONCLUSIONS: Povidone-iodine 1.25% ophthalmic solution was as effective as neomycin-polymyxin B-gramicidin for treating bacterial conjunctivitis, somewhat more effective against chlamydia, and as ineffective against viral conjunctivitis. Povidone-iodine ophthalmic solution should be strongly considered as treatment for bacterial and chlamydial conjunctivitis, especially in developing countries where topical antibiotics are often unavailable or costly.