Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.

Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. Design, Setting, and Participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. Main Outcomes and Measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection. Conclusions and Relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.

A randomized trial of levodopa as treatment for residual amblyopia in older children.

OBJECTIVE: To assess the efficacy and short-term safety of levodopa as adjunctive treatment to patching for amblyopia. DESIGN: Randomized, placebo-controlled trial. PARTICIPANTS: One hundred thirty-nine children 7 to 12 years of age with residual amblyopia resulting from strabismus, anisometropia, or both combined (visual acuity [VA], 20/50-20/400) after patching. METHODS: Sixteen weeks of oral levodopa or placebo administered 3 times daily while patching the fellow eye 2 hours daily. MAIN OUTCOME MEASURES: Mean change in best-corrected amblyopic-eye VA at 18 weeks. RESULTS: At 18 weeks, amblyopic-eye VA improved from randomization by an average of 5.2 letters in the levodopa group and by 3.8 letters in the placebo group (difference adjusted for baseline VA, +1.4 letters; 1-sided P=0.06; 2-sided 95% confidence interval, -0.4 to 3.3 letters). No serious adverse effects from levodopa were reported during treatment. CONCLUSIONS: For children 7 to 12 years of age with residual amblyopia after patching therapy, oral levodopa while continuing to patch 2 hours daily does not produce a clinically or statistically meaningful improvement in VA compared with placebo and patching.

Periocular hemangiomas and lymphangiomas.

Infantile hemangiomas are the most common benign tumor of childhood. Lymphangiomas are benign hamartomatous vascular tumors. Both lesions can be problematic when located in the periocular region. Pediatricians must be familiar with the characteristics of each which would necessitate referral to an ophthalmologist or other subspecialist for evaluation, including obstruction of the visual axis which can lead to amblyopia of the affected eye. Additional potential complications include proptosis, ocular motility limitation, optic nerve injury, and poor eyelid closure with or without corneal surface disease. All children with periocular hemangiomas or lymphangiomas should be referred to an ophthalmologist for further evaluation.

Office probing for treatment of nasolacrimal duct obstruction in infants.

PURPOSE: To determine whether demographic or clinical factors are associated with the outcome of office-based nasolacrimal duct probing for the treatment of congenital nasolacrimal duct obstruction (NLDO). METHODS: In two multicenter prospective studies, 384 eyes of 304 children aged 6 to <15 months with NLDO underwent a nasolacrimal duct probing performed in the office using topical anesthesia. Treatment success, defined as no clinical signs of NLDO (epiphora, increased tear lake, or mucous discharge) and no reoperation, was assessed 1 month after probing in one study and 6 months after probing in the other study. Data from both studies were pooled to evaluate associations between baseline characteristics and treatment success. RESULTS: Office probing was successful in 75% of eyes overall (95% CI, 70%-80%). The procedure was less successful in eyes of children with bilateral NLDO compared with unilateral NLDO (63% vs 80%; relative risk = 0.78 [95% CI, 0.66-0.92]) and in eyes that had 2 or 3 clinical signs of NLDO compared with one (71% vs 83%; relative risk = 0.88 [95% CI, 0.81-0.96]). Treatment success did not appear to be related to age, specific clinical signs of NLDO, prior treatment, or research study. CONCLUSIONS: Performing nasolacrimal duct probing in the office successfully treats NLDO in the majority of cases in children aged 6 to <15 months. The success rate is lower with bilateral disease or when more than one clinical sign of NLDO is present.

The effect of surgical preparation technique on the bacterial load of surgical needles and suture material used during strabismus surgery.

PURPOSE: To investigate the effectiveness of 3 surgical preparation techniques in decreasing bacterial contamination of needles and suture material during strabismus surgery. METHODS: Consecutive patients requiring 2-muscle strabismus surgery were randomized into 1 of 3 groups. In Group A, patients' periocular skin and bulbar conjunctivae underwent preparation with 5% povidone-iodine; the drape was placed without regard to eyebrows; and an open wire-loop lid speculum was used. Group B patients underwent the same preparation as Group A patients; however, the eyelashes and eyebrows were scrubbed with 5% povidone-iodine on cotton tip applicators, and the drape was placed to exclude the eyebrows from the surgical field. Group C patients underwent the same preparation as Group B patients; however, a bladed lid speculum was used during surgery to exclude some of the eyelashes from the surgical field. After the procedure, all needles and suture materials were sent separately for aerobic culture. The data were analyzed for differences in contamination rates between the groups. RESULTS: Of 77 patients, 24 (31.4%) had either a needle and/or suture contaminant. Groups A, B, and C had mean contamination rates of 29.6%, 34.6%, and 29.2%, respectively. There was no significant statistical variation in contamination among the 3 groups. The most common organism identified was a coagulase-negative staphylococcus strain. CONCLUSIONS: More meticulous sterile preparation of the surgical field did not result in a meaningful reduction in suture or needle contamination rates during strabismus surgery.

Treatment of symptomatic convergence insufficiency with a home-based computer orthoptic exercise program.

PURPOSE: To determine the efficacy of a home-based computer orthoptic program to treat symptomatic convergence insufficiency. METHODS: A retrospective review of consecutive patients with symptomatic convergence insufficiency treated with a home-based computer orthoptic program was performed. Symptomatic convergence insufficiency was defined as: near point of convergence (NPC) >6 cm, decreased positive fusional vergence, exophoria at near at least 4(Δ) greater than at far, and documented complaints of asthenopia, diplopia, or headaches with reading or near work. The Computer Orthoptics CVS program was used for this study. Before beginning the computer orthoptic program, patients with an NPC >50 cm were given 4 base-in prisms and push-up exercises (NPC exercises with an accommodative target) for 2 weeks. RESULTS: A total of 42 patients were included. Mean treatment duration was 12.6 weeks; mean follow-up, 8.5 months. Of the 42 patients, 35 were treated with the home-based computer orthoptic program and push-up exercises; the remaining 7 only used the computer orthoptic program. Because of a remote NPC, 5 patients were given base-in Fresnel prism before starting treatment. Baseline mean NPC was 24.2 cm; posttreatment mean NPC improved to 5.6 cm: 39 patients (92.8%) achieved an NPC of ≤6 cm (p < 0.001). Positive fusional vergence improved in 39 patients (92.8%). Fourteen patients reduced their near exophoria by ≥5(Δ). A total of 27 patients (64.2%) reported resolution of symptoms after treatment. CONCLUSIONS: In our study, home-based computer orthoptic exercises reduced symptoms and improved NPC and fusional amplitudes. The computer orthoptic program is an effective option for treating symptomatic convergence insufficiency.

Corneal power measurements in fixating versus anesthetized nonfixating children using a handheld keratometer.

PURPOSE: To compare keratometry measurements on a fixating patient with readings from the same nonfixating patient intraoperatively using the Nidek KM-500 handheld keratometer. METHODS: Consecutive patients who were scheduled for strabismus or nasolacrimal surgery between 5 and 11 years of age were included in the study. Handheld keratometry was performed preoperatively on both eyes with the child fixating and intraoperatively with the child anesthetized. Three readings were taken on each eye. The steepest and flattest corneal meridians were recorded. Intraclass correlation coefficients were calculated to assess reliability, and interchangeability was assessed by the use of the Bland-Altman method. RESULTS: Included in the study were 55 eyes of 28 patients. The average fixating keratometry reading was 44.10 +/- 1.45 D for right eyes and 44.12 +/- 1.42 D for left eyes. The average nonfixating keratometry reading was 44.06 +/- 1.62 D for right eyes and 44.02 +/- 1.54 D for left eyes. The intraclass correlation coefficient for the average keratometry obtained fixating versus nonfixating was 0.96 for right eyes and 0.95 for left eyes. The Bland-Altman analysis showed fairly large limits of agreement between readings, but most readings fall within the limits of variability. The mean time to obtain the intraoperative measurements was 4.26 minutes. CONCLUSIONS: In our study the Nidek KM-500 handheld keratometer provided reliable readings when used intraoperatively on anesthetized nonfixating children and required minimal time to perform.

Percutaneous drainage and ablation of orbital dermoid cysts.

BACKGROUND: Vision-threatening intraorbital dermoid cysts have traditionally been treated by complete surgical resection. Such radical surgical intervention may pose serious risks to both vision acuity and cosmesis. We describe a novel, minimally invasive approach for the treatment of orbital dermoid cysts. METHODS: This is an interventional retrospective case series. Two patients (17 and 4 years) presented with large intraorbital dermoid cysts. The first patient had a dumbbell-shaped lesion involving the temporalis fossa and superotemporal orbit. The second patient had a large, superior intraorbital lesion. Both patients presented with visual disturbance, globe displacement, and eyelid ptosis. A series of techniques were developed and implemented for percutaneous access, drainage, and catheter-based ablation (dual drug technique) of both orbital dermoid cysts. Initial access was gained with a 14-gauge angiocatheter needle system, followed by serial emulsification and drainage of the cyst contents. A 5-French catheter was coaxially placed for fluoroscopic contrast cyst definition and subsequent dual drug chemical ablation (sodium tetradecyl sulfate and ethanol). Suction drainage was maintained for 24 hours following ablation. RESULTS: Radiological and clinical evaluation demonstrated complete resolution of the dermoid cysts with no recurrence at 12-month follow-up in the first patient and 3 months in the second patient. Cosmetic results were excellent. Patients reported no pain and there were no neurologic, oculomotor, infectious, hemorrhagic, or other complications. CONCLUSIONS: Minimally invasive percutaneous drainage and ablation appears to be a promising treatment for large orbital dermoid cysts which would otherwise require extensive surgery to excise. Collaboration of an ophthalmologist and interventional radiologist is essential for evaluation, treatment, and follow-up.

The effect of media press coverage on parental preferences in amblyopia treatment.

BACKGROUND: Amblyopia has traditionally been treated by full-time occlusion of the sound eye. Recent studies have looked at the efficacy of atropine penalization and less patching in the treatment of amblyopia. These studies have drawn much attention from the lay press. This media attention may influence parent treatment preferences. METHODS: We distributed two news releases recently published by national newspapers to parents presenting to an outpatient pediatric eye clinic. They were then asked to rank atropine drops, 2-hour, 6-hour, and full-time patching (FTP) in order of preference. We then supplied additional information published in the scientific studies, but not mentioned in the lay press, and parents were asked to rerank their preferences. RESULTS: A total of 53 surveys were completed. The frequency with which each method (atropine, 2-hour, 6-hour, FTP) was initially ranked #1 was 66, 21, 2, and 11%, respectively. The frequency each was ranked #1 in the follow-up survey was 30, 26, 8, and 38%, respectively. The Wilcoxon matched-pair signed-ranks test demonstrated significant changes in treatment preferences (atropine, z = -4.204, P < 0.0001; 2-hour patch, z = -2.574, P = 0.0101; 6-hour patch, z = 4.484, P < 0.0001; FTP, z = 3.703, P = 0.0002). CONCLUSION: After having read press releases regarding amblyopia treatment, parents' preferences favored atropine and less patching. After being given additional information about the results of these studies, there was a strong shift in opinions in favor of more patching and away from atropine. The media appear to play an important role in influencing parent treatment preferences.

Resident glaucoma surgical training in United States residency programs.

PURPOSE: To determine current trends in resident glaucoma surgical training throughout the United States. METHODS: A comprehensive survey was sent to the residency director of all 121 ACGME-accredited ophthalmology training programs in the United States. RESULTS: The mean and median number of glaucoma procedures a resident will complete by the end of their training is 8.6 and 8 respectively for trabeculectomy, 5.3 and 4 for combined trabeculectomy/phacoemulsification, and 3.6 and 2 for tube-shunts. One percent of residents will gain experience as primary surgeon on trabeculectomies during their first year, 32% during their second year, and 67% during their third year. Seventy-five percent of residents are taught more than one trabeculectomy technique by more than one staff surgeon. Eighty-four percent of residents are taught glaucoma surgery almost exclusively by fellowship-trained glaucoma surgeons. Eighty-two percent of residents use antimetabolites (mitomycin C or 5-FU) as an adjunct to trabeculectomy most or all of the time. More than 96% of resident tube-shunt procedures use Ahmed, Baerveldt, or Molteno devices. Eighty percent of residents do not perform any pediatric glaucoma surgeries. Sixty-two percent of residents rotate out of their main facility to perform glaucoma surgery. CONCLUSIONS: Residents are being exposed to glaucoma surgery early in their residency training. Most are performing a variety of different procedures and techniques, and are taught by fellowship-trained surgeons. Residents gain very little exposure to pediatric glaucoma surgery. All programs reported compliance with minimum RRC requirements for glaucoma filtering surgery.