Gut Microbiome and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, is strongly associated with gestational age and weight at birth. Yet, many extremely preterm infants never develop ROP or develop only mild ROP with spontaneous regression. In addition, a myriad of other factors play a role in the retinal pathology, one of which may include the early gut microbiome. The complications associated with early gestational age include dysbiosis of the dynamic neonatal gut microbiome, as evidenced by the development of often concomitant conditions, such as necrotizing enterocolitis. Given this, alongside growing evidence for a gut-retina axis, there is an increasing interest in how the early intestinal environment may play a role in the pathophysiology of ROP. Potential mechanisms include dysregulation of vascular endothelial growth factor and insulin-like growth factor 1. Furthermore, the gut microbiome may be impacted by other known risk factors for ROP, such as intermittent hypoxia and sepsis treated with antibiotics. This mini-review summarizes the literature supporting these proposed avenues, establishing a foundation to guide future studies.

Proximal tarsal attachments of the levator aponeurosis: implications for blepharoptosis repair.

PURPOSE: To examine the tarsal attachments of the levator aponeurosis. DESIGN: Experimental anatomic study. PARTICIPANTS: Sixteen orbits from 12 fresh frozen white cadavers. METHODS: Eight specimens served as controls. In the remaining 8 specimens from 4 cadavers, the upper eyelid was everted. All specimens then were fixed in formalin. The age, sex, and laterality were recorded in both groups. The eyelid lamellae and tarsal attachments of the levator aponeurosis in particular were examined microscopically. Lamellar and nonlamellar ocular anatomic features and the relationships of the preaponeurotic and postaponeurotic spaces were measured. MAIN OUTCOME MEASURES: Histologic findings of the extent and pattern of the tarsal attachments of the levator aponeurosis in relation to the tarsus and Müller's muscle and of the changes in the lamellae in eyelid eversion. RESULTS: The demographic and baseline anatomic characteristics of both the noneverted control and everted eyelid groups were similar. In comparing everted with noneverted controls, the preaponeurotic space was significantly shorter (6.22 and 10.61 mm, respectively; P = 0.003) and the preaponeurotic-to-postaponeurotic space ratio was halved (0.57 and 1.16, respectively; P = 0.005). Although the distance from the superior tarsal border to Whitnall's ligament increased significantly in everted versus noneverted eyes (14.65 and 11. 03 mm, respectively; P = 0.016), there was no significant difference in the length of postaponeurotic space in the 2 groups (11.07 and 9.69 mm, respectively; P = 0.370). The levator aponeurosis attached to the anterior tarsus in both groups. The proximal point of attachment was the superior border of the tarsal plate, adjacent to the insertion of Müller's muscle tendon. CONCLUSIONS: The deeper aponeurotic fibers and Müller's muscle attach proximally at the superior tarsal border. Upon eyelid eversion, the 2 lamellae move as a unit and the postaponeurotic space remains stable. A proximal tarsal attachment suggests that blepharoptosis procedures that advance an involutional or disinserted levator aponeurosis onto to the superior tarsus approximate that aspect of native anatomic features. In addition, posterior surgical approaches that address Müller's muscle may involve resections in closer proximity to the aponeurosis than previously thought. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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).

Refractive outcomes comparing primary laser to primary bevacizumab with delayed laser for type 1 ROP.

PURPOSE: To compare the refractive outcomes of intravitreal bevacizumab (IVB) and delayed peripheral retinal photocoagulation (PRP) with primary PRP in infants treated for posterior type 1 ROP. METHODS: The medical records of 87 infants at a tertiary referral center treated for posterior type 1 ROP between 2006 and 2016 were reviewed retrospectively. Consecutive infants received primary PRP before and primary IVB after a change in treatment practice implemented in early 2011. In most cases primary IVB was supplemented with prophylactic laser treatment after 60 weeks' PMA (IVB-PRP). The main outcome was spherical equivalent (SE) in diopters, determined by cycloplegic refraction between 2 and 4 years. Infants treated with IVB-PRP were also compared to the those who received only IVB as monotherapy. RESULTS: The final analysis included 34 eyes of 19 infants in the primary PRP group and 40 eyes of 21 infants in the IVB-PRP group. Mean SE was -7.4 ± 5.2 D in the primary PRP group and -0.16 ± 2.2 D in the IVB-PRP group (P < 0.001). This relationship persisted after stratification by zone of ROP and the presence of aggressive posterior ROP. There was no statistically significant difference in mean SE between the IVB-PRP group and the 8 eyes of 4 infants who received IVB as monotherapy. Of 46 infants who received primary IVB, 37 completed an examination under anesthesia after 60 weeks' PMA. In these patients, 70% of eyes showed peripheral vascular leakage on fluorescein angiography. CONCLUSIONS: In our study cohort, infants treated with IVB-PRP were significantly less myopic than those treated with primary PRP. Delayed laser after 60 weeks' PMA, in hopes of reducing the risk of late reactivation with retinal detachment, did not negate the refractive benefits of primary IVB.

Neurodevelopmental Outcomes Comparing Bevacizumab to Laser for Type 1 ROP.

BACKGROUND AND OBJECTIVE: To evaluate neurodevelopmental outcomes among infants treated for retinopathy of prematurity (ROP) at the authors' institution. PATIENTS AND METHODS: Before-and-after retrospective chart reviews identified 40 infants treated with laser and 46 treated with primary intravitreal bevacizumab (IVB). Primary outcomes were death, hearing loss, bilateral visual impairment (BVI), and cerebral palsy (CP); odds ratios (ORs) were calculated to determine factors associated with CP. Secondary outcomes were mean Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores. RESULTS: Overall, there were no significant differences in primary outcome measures by treatment group. However, adjusted odds of BVI were significantly higher with laser compared to IVB (OR = 13.1; P = .038). Although IVB was not associated with CP, both hydrocephalus and BVI were strongly correlated with CP. Mean Bayley-III scores were similar when comparing nine laser-treated infants to 13 IVB-treated infants. CONCLUSIONS: Visual outcomes are an important aspect of neurodevelopment. IVB was not associated with severe developmental disabilities and may protect against vision loss in this analysis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:337-343.].

Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma.

BACKGROUND: Retinoblastoma is the most common intraocular tumor of childhood. Vision salvage rates in advanced cases are less than ideal, and the optimal treatment for intraocular retinoblastoma has not been established. We report the results of an institutional retinoblastoma treatment trial to determine the vision salvage rates and toxicity of a regimen combining carboplatin and etoposide with focal retinal therapy. PROCEDURE: Twenty-nine patients diagnosed with retinoblastoma in 48 eyes were treated between 1992 and 2004 with at least six cycles of carboplatin and etoposide combined with focal retinal therapy. RESULTS: The response rate of eyes after six cycles of chemotherapy was 85.4%. Twenty-two eyes were enucleated, but only seven eyes received EBRT. The vision salvage rate without EBRT was 82.6% for eyes with Reese-Ellsworth (R-E) groups I-IV tumors and 20% for eyes with R-E group V tumors. The vision salvage rate without EBRT for eyes with Murphree groups A and B tumors was 77.3% but was only 26.9% for eyes with groups C and D tumors. Acute side effects were minimal. CONCLUSIONS: The combination of carboplatin and etoposide with focal therapy is a well-tolerated regimen that has acceptable vision salvage rates for R-E groups I-IV and Murphree groups A and B retinoblastoma. This combination avoids the use of EBRT and the toxicity of additional chemotherapy agents. However, patients with R-E group V and Murphree groups C and D retinoblastoma have poorer outcomes and require more intensive therapy.

Cataracts in congenital toxoplasmosis.

PURPOSE: To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS: Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS: In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS: In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.

Refractive abnormalities in childhood.

The knowledgeable pediatrician can make a significant contribution to the management of refractive errors by aiding in the early recognition of abnormalities, making appropriate referrals, and reinforcing the ophthalmologist's recommendations to the family. If this article has focused the reader's attention and caused a few rays of light to fall on an important subject, it has achieved its purpose.

Eyelid eversion for visualisation of the upper eyelid lamellae: an anatomical cadaver study.

Controversy persists in surgical eyelid anatomy despite the routine use of microanatomical examination in modern eyelid research. The aim of our study was to facilitate visualisation of upper eyelid anatomy by optimising the orientation of cadaveric specimens. We studied the anatomy of everted eyelids, providing an excellent histological view of the posterior approach to the eyelid commonly used in surgery. Non-traumatic separation of the eyelid lamellae provides a new view of the eyelid's lamellar nature. Further application of this model may enhance understanding of the multilayered aspect of the levator aponeurosis. The technique may improve intraoperative understanding of critical eyelid anatomy and promote safer and more effective eyelid surgery.

When may the posterior capsule be preserved in pediatric intraocular lens surgery?

PURPOSE: To refine indications for primary posterior capsulotomy (PPC) in conjunction with posterior chamber intraocular lens (PCIOL) implantation for cataract in childhood. DESIGN: Noncomparative case series. PARTICIPANTS: Patients 1 to 13 years old who underwent cataract extraction with intent to preserve the posterior lens capsule and PCIOL implantation between January 1992 and December 1998 at a pediatric hospital. METHODS: Medical records were reviewed to determine the frequency and timing of posterior capsule opacification (PCO) after PCIOL surgery with preservation of an intact posterior capsule. Comparison of pseudophakic PCO rates for groups defined by age and several possible risk factors. Assessment of safety and efficacy for PPC with anterior vitrectomy performed through a limbal incision in cases where the posterior capsule could not be preserved. MAIN OUTCOME MEASURES: Need for neodymium:yttrium-aluminum-garnet laser capsulotomy or surgical membranectomy to treat PCO. RESULTS: PCO occurred in 40% of 30 eyes with intact posterior capsule. Mean follow-up duration was 22 months for eyes that had PCO develop and 24 months for those in which the posterior capsule remained clear. Laser capsulotomy was required for 64% of 14 eyes in the 1- to 6-year-old age range but for only 19% of 16 in the 6- to 13-year-old range (P < 0.05). Mean time from surgery to PCO was 7 months for the younger group and 13 months for the older group. A need for repeated capsulotomy (one eye) or membranectomy with anterior vitrectomy (two eyes) was found only in the younger age group. There was no association of PCO with trauma history, cataract type, residual lens cortex, IOL position, or postoperative fibrin clot. Final vision was possibly compromised as a result of PCO in one eye with amblyopia. None of 24 eyes in which PPC with anterior vitrectomy was performed out of intraoperative necessity before primary PCIOL implantation had secondary opacification develop. No reduction in postoperative vision was attributable to PPC. CONCLUSIONS: PPC seems to be advisable for children less than 6 years old when cataract extraction with PCIOL implantation is performed. Preservation of the posterior capsule remains appropriate for older children with pseudophakia.

Rhegmatogenous retinal detachments in children: risk factors and surgical outcomes.

PURPOSE: To describe the presenting features and surgical outcomes in a series of children with rhegmatogenous retinal detachments. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Thirty-nine eyes of 34 children 18 years of age or younger undergoing surgery for rhegmatogenous retinal detachment. METHODS: Patients were identified by chart review at two affiliated tertiary care centers. Risk factors for retinal detachment were classified into four categories: (1). congenital or developmental structural ocular abnormalities, (2). trauma, (3). previous ophthalmologic surgery, and (4). preceding uveitis. RESULTS: Median age was 10 years, and 79% of patients were boys. Nine patients (26%) had bilateral retinal detachment at presentation, or experienced a detachment in their second eye before their nineteenth birthday. Every eye had at least one risk factor for retinal detachment, and more than half had risk factors in two or more categories. Structural abnormalities were most common (56%). Fifty-one percent of eyes underwent previous surgery, 36% experienced trauma, and 15% had uveitis. Detachments tended to be complex. Median follow-up was 24 months. Retinal reattachment was achieved in 79% of eyes; however, visual recovery was modest. Median preoperative and postoperative visual acuities were counting fingers and 20/400, respectively. Predictors of a poor visual outcome were: unmeasurable or light perception-only preoperative vision (P = 0.0001), macula-off retinal detachment (P = 0.01), the need for vitrectomy surgery (P = 0.01), the presence of proliferative vitreoretinopathy grade C or worse (P = 0.02), and the use of silicone oil (P = 0.02). CONCLUSIONS: Predisposing factors in pediatric retinal detachments, particularly congenital and developmental structural abnormalities, may be more common than previously reported. Modern vitreoretinal surgical techniques can help achieve retinal reattachment in most cases. Many factors contribute to the limited visual recovery in this patient population. Predictors of visual outcomes are similar to those observed in adults. Inability of the clinician to determine confidently the preoperative visual acuity is a newly identified predictor of poor visual outcomes.