Influence of Pre- and Intraoperative Local Anaesthetic in Strabismus Surgery under General Anaesthesia in Adults.

BACKGROUND: As studies have shown a reduction in the occurrence of the oculocardiac reflex with the addition of local anaesthesia, we changed our care regime accordingly a few years ago. To promote and establish better patient care, we retrospectively analysed the files of our patients who underwent strabismus surgery from 2013 to 2021 in order to compare strabismus surgery under general anaesthesia with and without local anaesthetics in a routine clinical setting. PATIENTS AND METHODS: Data from 238 adult patients who had undergone strabismus surgery could be extracted from the files: G1: n = 102, only general anaesthesia; G2: n = 136, preoperative application of tetracaine eye drops and intraoperative subtenon lidocaine/levobupivacaine in addition to general anaesthesia. We compared the two groups in regard to the frequency of oculocardiac reflex, the amount of atropine needed to treat, as well as the amount of antiemetic and analgesic medication given, and time spent in the recovery room. RESULTS: Mean age of G1 was 50 years and 52 years in G2. There was no significant difference between the kind of surgeries (recessions/resections), the number of patients who had undergone a reoperation, or the duration of the operations. Adding local anaesthetics resulted in significantly less occurrence of oculocardiac reflex (p = 0.009), a reduction in the need for atropine, analgesic, or antiemetic medication, as well as reduced time in the recovery room. CONCLUSION: As this increases patient safety and comfort and is cost-effective (less time in the recovery room), we recommend adding perioperative local anaesthesia to strabismus surgery performed under general anaesthesia.

Strabismus Surgery: A Retrospective Comparison of Different Postoperative Treatment Regimes to Prevent Infections.

BACKGROUND: As studies have shown postsurgical polyvidone-iodine to be at least equal to postsurgical topical antibiotics, our postsurgical care regime was adjusted accordingly in 2017. Here, we retrospectively compared the postsurgical infection rate in patients who underwent strabismus surgery prior to and following this change in regimen in a routine clinical setting. PATIENTS AND METHODS: In this retrospective and explorative study, data from 162 adult patients who had undergone strabismus surgery was extracted from files: 98 patients who had received topical gentamycin in a combination ointment with steroid (postsurgery) followed by 1 week of topical gentamycin with nonsteroidal antiphlogistic eye drops for 1 week (group 1) and 64 who had received polyvidone-iodine once immediately postsurgically instead. We compared both groups' postsurgical healing period regarding occurrence of bacterial conjunctival infection and conjunctival swelling and redness as well as other complications. Data were extracted from the entries of the routine follow-up dates on postsurgical days 1, 7, and at 3 months. RESULTS: Mean age of group 1 was 49 years and 51 years in group 2. There was no significant difference between the kind of surgeries (recessions/resections) or the number of patients who had undergone a reoperation. There was no significant difference between the groups for any of the endpoints analyzed at any of the three regular follow-up dates. From group 1, 12.04% and from of group 2, 6.25% showed bacterial conjunctivitis 1 week postsurgery. There was no endophthalmitis. CONCLUSION: Topical polyvidone-iodine given once at the end of strabismus surgery is a good alternative to topical antibiotics with a comparable healing progress. It carries a comparable risk of infection as seen with a 1-week course of topical antibiotics. The advantages are less manipulation of the eye, no bacterial resistance caused, and cost efficiency. In addition, the lack of anti-inflammatories given in group 2 did not pose a disadvantage.

Comparing Botulinum Toxin Injections with Extraocular Muscle Surgery in Toddlers with Esotropia: A Retrospective Analysis.

BACKGROUND: In toddlers with esotropia, early alignment of the visual axes either with extraocular muscle surgery (EOMS) or botulinum toxin injections (BTIs) into both medial rectus muscles may result in improved depth perception. We compared the outcome of BTIs with EOMS in toddlers in order to gain further insight into the advantages and disadvantages of either method. PATIENTS AND METHODS: In this retrospective study, our encrypted database was searched for toddlers with esotropia aged 35 months or younger at the time of initial treatment with either BTIs or EOMS and who had a follow-up of at least 2 years. We analyzed the angle of deviation, dose effect (DE), and binocularity as well as the number of interventions. RESULTS: We identified 26 toddlers who received their first treatment for esotropia within the first 35 months of life: 16 with BTIs (9 males, 7 females) and 10 with EOMS (3 males, 7 females). Mean follow-up was considerably longer in the EOMS (87.7 months) than in the BTI group (35.7 months). Age at first intervention was 22.8 months in the BTI and 24.1 months in the EOMS group, and each toddler wore its full cycloplegic refraction. Mean angle at treatment was 41.25 prism diopters (PD) in the BTI compared to 52.9 PD in the EOMS group. The BTI group received an average of 1.68 BTIs, with a mean dosage of 14.5 IU Botox and a mean DE (mDE) of 1.8 PD/IU. In the EOMS group, the average number of surgeries was 1.4, with a mean dosage of 16.85 mm and a mDE of 3.14 PD/mm surgery. Some degree of binocularity could be observed in 9 (56%) of the BTI (5 × Bagolini positive, 2 × 550″, 2 × 220″) and in 4 (40%) of the EOMS group (2 × 3600″, 1 × 550″, 1 × 300″). By the end of the BTI group follow-up, four toddlers electively underwent EOMS rather than a 3rd BTI (followed by a 3rd BTI in 1), which resulted in the appearance of measurable binocularity in all four (1 × Bagolini positive, 1 × 220″, 1 × 200″, 1 × 60″). CONCLUSIONS: Our results show that BTIs are a viable treatment alternative in early esotropia. Even if EOMS is ultimately required, some binocularity may develop as the visual axes are aligned for some time in the sensitive phase owing to the effects of Botox. Moreover, less surgical dosage is needed than would have otherwise been necessary to treat the original angle of deviation. BTIs are faster, less invasive, and present as an effective alternative when patient compliance is too low to reliably measure the angle of deviation, which is essential for the planning of EOMS.

Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes.

Purpose: The aim of this study was to investigate the molecular basis of childhood glaucoma in Switzerland to recommend future targeted genetic analysis in the Swiss population. Methods: Whole-exome sequencing and copy number variation (CNV) analysis was performed in a Swiss cohort of 18 patients from 14 unrelated families. Identified variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification. Breakpoints of structural variants were determined by a microarray. A minigene assay was conducted for functional analysis of a splice site variant. Results: A diagnosis of primary congenital glaucoma was made in 14 patients, of which six (43%) harbored pathogenic variants in CYP1B1, one (7%) a frameshift variant in FOXC1, and seven (50%) remained without a genetic diagnosis. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome harbored a FOXC1 duplication plus an additional FOXC1 missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. A diagnosis of juvenile open-angle glaucoma was made in one patient, and genetic analysis revealed a FOXC1 duplication. Conclusions: Sequencing of CYP1B1 and FOXC1, as well as analysis of CNVs in FOXC1, should be performed before extended gene panel sequencing. Translational Relevance: The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families.

Strabismus Surgery of Consecutive Exotropia.

PURPOSE: The purpose of this study was to determine the surgical outcome, dose-effect (DE), and degree of binocularity in patients undergoing surgery for consecutive exotropia following initial surgery of esotropia. PATIENTS/METHODS: Twenty-one patients were identified. We analyzed the mean angle of deviation pre- and postoperatively as measured with the alternate prism cover test, DE, and binocularity. RESULTS: All patients had had previous strabismus surgery. The surgery for consecutive exotropia had been performed at a mean age of 35.92 ± 18.26 years. In 19 of these patients, surgery of consecutive exotropia involved at least one previously operated extraocular muscle, and the mean interval to the previous surgery was 25.67 ± 16.14 years. The mean angle of deviation (DE) at distance and in the primary position was - 33.43 ± 12.75 prism diopters (PD) preoperatively, + 0.76 ± 7.91 PD 1 week after surgery, and - 7.24 ± 12.14 PD 3 months after surgery. The mean DE was 3.58 ± 1.53 mm/PD at 1 week and 2.70 ± 1.78 mm/PD at 3 months post-surgery. Postoperatively, 62% patients had a binocularity of at least Bagolini positive, 33% had either a positive TNO or Titmus Test, and 24% were Lang I positive (550″). CONCLUSION: Performing strabismus surgery with consecutive exotropia results in restoration of some binocularity in a large number of patients, even in adults, and should be considered as a possibility. The dose-effect is comparable to conventional surgery of exotropia.

Congenital fixed dilated pupils due to ACTA2- multisystemic smooth muscle dysfunction syndrome.

Congenital fixed dilated pupils (congenital mydriasis) is characterized by hypoplasia or aplasia of the iris muscles, with absence of iris between the collarette and pupillary border, creating a scalloped pupillary margin. This condition has been reported in a multisystemic smooth muscle cell dysfunction syndrome, combined with congenital patent ductus arteriosus, cerebrovascular disease (Moya-moya-like), coronary artery disease, thoracic aorta aneurysm, and dysfunction of smooth muscle cells in organs throughout the body. All affected individuals carry a p.R179H heterozygous mutation in the ACTA2 gene. We add to the ophthalmologic involvement with 3 more patients. Congenital fixed dilated pupils is a rare condition and should alert ophthalmologists to the possibility of the coexistence of systemic life-threatening disorders.

Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes.

PURPOSE: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. METHODS: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. RESULTS: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III:1; III:2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2) and in unaffected I:1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. CONCLUSIONS: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.

Expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations.

PURPOSE: Anterior segment dysgenesis (ASD) comprises a heterogeneous group of developmental abnormalities that affect several structures of the anterior segment of the eye. The main purpose of this study was to assess the proportion of FOXC1 and PITX2 mutations and copy number changes in 80 probands with ASD. METHODS: The patients were examined for FOXC1 and PITX2 copy number changes and mutations using MLPA (multiplex ligation-dependent probe amplification) and direct sequencing. Subsequently, the identified copy number changes were fine-mapped using high-resolution microarrays. In the remaining mutation-negative patients, sequencing of the FOXC1 andPITX2 3' untranslated regions (UTRs) and three other candidate genes (P32, PDP2, and FOXC2) was performed. RESULTS: Thirteen FOXC1 and eight PITX2 mutations were identified, accounting for 26% (21/80) of the cases. In addition, six FOXC1 and five PITX2 deletions were found, explaining 14% (11/80) of the cases. The smallest FOXC1 and PITX2 deletions were 5.4 and 1.6 kb in size, respectively. Six patients carrying FOXC1 deletions presented with variable extraocular phenotypic features such as hearing defects (in 4/6) and mental retardation (in 2/6). No further genetic defects were found in the remaining mutation-negative patients. CONCLUSIONS: FOXC1 and PITX2 genetic defects explain 40% of our large ASD cohort. The current spectrum of intragenic FOXC1 and PITX2 mutations was extended considerably, the identified copy number changes were fine mapped, the smallest FOXC1 and PITX2 deletions reported so far were identified, and the need for dedicated copy number screening of the FOXC1 and PITX2 genomic landscape was emphasized. This study is unique in that sequence and copy number changes were screened simultaneously in both genes.

LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma.

The latent TGFbeta-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGFbeta-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients.

Corneal opacities in the Hallermann-Streiff syndrome.

We present six patients with typical Hallermann-Streiff syndrome. All have microphthalmia and were operated for congenital cataract. Three of the patients developed a severe glaucoma and one patient presented repeated uveal effusions. Five of our patients have the same pattern of corneal stromal opacities. The opacities are ill defined and bilateral; the stroma between the opacities is clear. The opacities are observed in two children around the age of 5. Follow up of 10 years did not reveal a manifest increase of the lesions. The authors believe that corneal stromal opacities are a feature of the Hallermann-Streiff syndrome and they would urge ophthalmologists to look for this.