Bruce Schnall

Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1

BackgroundCongenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A.ResultsSixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.ConclusionAnalysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.

Conservative Treatment of Congenital Dacryocele

PURPOSE To study prospectively the effectiveness of medical management of congenital dacryoceles. METHODS All patients presenting with congenital dacryocele that were not infected were treated with warm compresses, massage, and topical antibiotics. Dacryoceles that did not resolve with at least two weeks of medical management were probed. Dacryoceles that were infected were treated with intravenous (IV) antibiotics in addition to warm compresses and massage. RESULTS Seventeen patients with 21 dacryoceles were studied over a 3 1/2-year period. All patients were examined by the authors and treatment was initiated prior to 3 weeks of age. Sixteen dacryoceles resolved with medical management in 1 to 6 days. Three of these 16 dacryoceles were infected and patients were hospitalized at the time of initial ophthalmic evaluation (2 to 4 days of life). One additional dacryocele became infected after 2 days of medical management (4th day of life), requiring hospital admission and IV antibiotics. All four infected dacryoceles resolved within 24 hours of the initiation of IV antibiotics, warm compresses, and massage. Five dacryoceles were probed after not resolving within 14 to 31 days of medical management. One dacryocele required a repeat probing. CONCLUSIONS Medical management can be effective in the treatment of congenital dacryoceles; 76% of dacryoceles in this series resolved after 6 days of medical management.

A strabismus susceptibility locus on chromosome 7p

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes.

Unilateral keratitis following death of a twin as the presenting sign of herpetic infection in a neonate

Neonatal herpes simplex virus (HSV) manifests as a disease limited to skin, eyes, and/or mucous membranes, central nervous system disease with/without skin involvement, or disseminated infection. Given the high morbidity and mortality of untreated neonatal HSV, early recognition and prompt treatment are important. We report two cases of unilateral HSV keratitis, after Cesarean section, in neonates whose twin had died. Both mothers denied history of HSV. Ophthalmic diagnosis led to full systemic workup and appropriate treatment.

Sequential Bilateral Dacryocele

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A pilot study using electronic reminders for amblyopia treatment

ABSTRACT Treatment compliance is the most important factor for predicting a successful outcome in amblyopia treatment. Electronic applications have been successfully employed in other medical conditions in an effort to improve compliance. Aim: To determine whether a smartphone medical adherence application (app) (RxmindMe® Prescription/Medicine Reminder and Pill Tracker) may be successfully incorporated into the treatment plan of patients 3–7 years of age who have not previously been treated for amblyopia. Methods: Children 3–7 years of age were randomized to receive electronic reminders (reminders group) or standard instructions (control group). Visual acuity and compliance with treatment was assessed at the first follow-up visit. The child’s adherence with the prescribed treatment was calculated as the reported number of hours of patching performed divided by the number of hours prescribed or compliance percentage. The validated “Amblyopia Treatment Index Parental Questionnaire” was administered to the parent/guardian to assess any differences in the compliance subscale between the two treatment groups. Any difficulties encountered with the use of the reminder app were also recorded at the follow-up visit. Results: Twenty-four participants were enrolled. Twelve participants in the reminder group (eight female, four male; mean age 4.5 ± 1.3) were compared with 12 participants in the control group (five female, seven male; mean 4.8 ± 1.1). No significant differences were found between the two groups in terms of age (p = 0.62), gender (p = 0.22), or degree of amblyopia at the start of treatment (p = 0.99). Eleven of 12 participants in the reminders group were able to incorporate the reminder app into amblyopia treatment. No participant reported malfunction of the alarm portion of the reminder app. There was no significant difference seen in degree of visual acuity improvement, reported percentage compliance or effect on the compliance subscale as assessed by the ATI questionnaire. Several participants reported the app to be “helpful” in initiating treatment. Conclusion: Our findings indicate that use of a smartphone app is feasible in this patient population. Targeting the app to specific patient demographics or when difficulty with compliance is encountered needs to be further investigated.

Impact of a Strabismus Surgery Suture Course for First- and Second-Year Ophthalmology Residents

PURPOSE To investigate the effectiveness of an eye muscle surgery course on first- and second-year postgraduate ophthalmology residents. METHODS This prospective cohort pilot study invited first- and second-year ophthalmology residents to participate in a 2-hour strabismus surgery course at Wills Eye Hospital. The course consisted of a didactic session followed by a wet laboratory session. The wet laboratory session simulated strabismus surgery using a model constructed of chicken breast followed by partial-thickness scleral suture passes in pig eyes. A structured self-assessment evaluation form and a questionnaire in the validated Ophthalmology Surgical Competency Assessment Rubric approved by the International Council of Ophthalmology (ICO-OSCAR:strabismus) were used to assess the effectiveness of the course. RESULTS A total of 12 residents, 8 (67%) first-year and 4 (33%) second-year, were enrolled for this survey. Following the course, most residents felt less anxious (73%). All residents responded that the course was helpful or somewhat helpful in preparation for strabismus surgery. Regarding the distribution of ratings on questions of subjective experience, knowledge of steps, and understanding of potential complications, the residents gave significantly higher ratings after the course (P < .029). The change in the modified ICO-OSCAR:strabismus assessments mean score was statistically significant before and after training (P = .038). CONCLUSIONS A strabismus course can play an important role in preparing residents for strabismus surgery. [J Pediatr Ophthalmol Strabismus. 2017;54(6):339-345.].

Clinical Evaluation of Four-Muscle Tenotomy Surgery for Nystagmus

PURPOSE To document prospectively the effect of four-muscle tenotomy surgery on visual acuity (VA) and nystagmus intensity and assess, by the use of a questionnaire, the experience of adult patients and the parents of children who have had the four-muscle tenotomy procedure for nystagmus in the absence of strabismus or an anomalous head position. The qualitative perceived benefits or lack thereof from the procedure were compared to the subjective effects on nystagmus intensity and VA. METHODS Fifteen patients diagnosed as having congenital/infantile or acquired nystagmus, including albinism or other visual sensory disorders without anomalous head positions or coexisting strabismus, were included in this study. The changes in preoperative and postoperative VA and nystagmus were evaluated based on clinical and perceptual measurements and video recordings. RESULTS All 15 patients had preoperative and postoperative ophthalmological examinations. One patient had a postoperative conjunctival cyst, which was successfully removed. Fourteen patients (93%) showed clinical VA improvement in at least one eye. Fourteen patients were video recorded preoperatively and postoperatively to analyze their nystagmus intensity; case 9 was not included. Postoperatively, 10 patients (71%) showed a decrease in nystagmus intensity. Thirteen patients (87%) perceived vision improvement and 11 patients (73%) perceived a decrease in nystagmus intensity. All patients experienced either clinically improved VA or a decrease in nystagmus intensity. Fourteen patients (93%) perceived either improved VA or a decrease in nystagmus intensity. The preoperative and postoperative changes in VA (P = .002) and nystagmus intensity (P = .043) were both statistically significant. CONCLUSIONS The authors have shown that four-muscle tenotomy surgery for nystagmus can improve VA and decrease nystagmus intensity. The study yielded subjective patient satisfaction, modest objective improvement in VA, and no significant complications.

What does convergence insufficiency look like to the strabismologist

Purpose: The purpose of this retrospective chart review is to delineate what convergence insufficiency looks like to a strabismologist. By classifying the entity, determining the most prevalent symptoms and findings of the disease, a standard will be set for further research into the disease patterns and treatment parameters. Conclusion: Our study suggests that CI can present in ways that are not expected. Symptoms: A large number of our patients were asymptomatic at presentation. The presence or absence of strabismus may not play a role in the diagnosis of CI Up to 8% of patients who have been diagnosed with CI were described by some strabismologists as esotropic or esophoric. 20% of patients had a NPC of 1 cm Fusional amplitudes may play a role in diagnosis of CI, data has been collected, results pending.

When to treat congenital esotropia.

Nelson: We’re going to discuss when to treat congenital esotropia. A 6-month-old child comes into your office with an esotropia of 65 prism diopters, alternate fixation, and a cycloplegic refraction of +2.50. Dr. Morrison, what is your treatment plan? Morrison: A child who’s clearly alternating fixation has a large angle of deviation that I assume to be an infantile strabismus. My cutoff for prescribing glasses would be +2.50 or +3.00. I would consider trying glasses if the child had any accommodative component and certainly if there was a significant near-distance disparity, but routinely this is a child who would progress to surgery. When you discuss surgical correction of infantile esotropia there are two issues that have generated argument in the past. One is whether you should proceed with early surgery to improve longterm stereopsis potential. The second issue is the stability of the strabismus angle. If you observe a child with infantile strabismus over time, many times the angle will slightly increase, which may be associated with some contraction of the medial rectus muscle. Some have argued waiting until the strabismic angle is stable before proceeding with surgery. My current practice pattern would be to schedule that child for surgery. With a deviation of 65 or less, I would do a bilateral medial rectus recession. I would not do a lateral rectus resection with an angle of 65 in a child younger than 2 years. I would see the child again a week prior to surgery. If the angle was stable or within 10 prism diopters, especially if it was increasing slightly, I would proceed with my regular surgery. If I felt that the angle was significantly less, I would delay the surgery for an additional set of measurements to be sure that the angle is stable. Nelson: Dr. Young, same question. Young: My approach would be similar. I do think you need two examinations to make sure that the alignment is stable. It’s been my experience that some of these children get better. If they come to our office at 3 months of age with a 30-prism diopter esotropia, it’s not terribly uncommon for that angle to be smaller and occasionally zero when they return a few months later. So we do need to make sure the alignment is stable, and the Congenital Esotropia Observational Study (CEOS) showed that we need to proceed with caution for the smaller angles. If the angle is 40 prism diopters or more, the CEOS showed that it’s unlikely to get better on its own. I agree with Dr. Morrison that if the hyperopia is 3 prism diopters or less, glasses for the hyperopia are unlikely to reduce the esotropia significantly. So I would also operate if the angle was stable with two consecutive examinations a month or more apart. Nelson: Dr. Schnall, same question. Schnall: In the congenital esotropia observational study, the largest esotropia they observed to resolve without treatment was 45 diopters. Therefore, you can be fairly confident that this patient’s large esotropia is not going to resolve without surgical treatment. I agree with examining the child a second time and I think you also David G. Morrison, MD, is from the Department of Ophthalmology, Vanderbilt University, Nashville, Tennessee.