Refractive error in unilateral Duane syndrome.

PURPOSE: To investigate whether chronic co-contraction of the medial and lateral rectus muscles leads to higher against-the-rule astigmatism in affected versus fellow eyes in Duane syndrome. METHODS: A database of 4,103 patients of Dr. Arthur Jampolsky was queried for diagnosis of Duane syndrome. Inclusion criteria were unilateral Duane syndrome and complete data set. Refractive error was compared between Duane and fellow eyes. RESULTS: A total of 84 patients with unilateral Duane syndrome were identified. The spherical equivalent of Duane eyes and fellow eyes was similar (0.4 vs. 0.2 [P = 0.14]). Mean cylinder power was higher in Duane eyes compared to fellow eyes (0.7 vs 0.4 [P = 0.0003]). There was modest evidence of more against-the-rule astigmatism in Duane eyes compared to fellow eyes (P = 0.04) but no difference for with-the-rule astigmatism (P = 0.83). Duane compared to fellow eyes were, however, significantly more likely to have oblique astigmatism (P = 0.004) or any astigmatism at all (P = 0.0005). CONCLUSIONS: Duane eyes compared to fellow eyes had higher astigmatism that was more likely to be oblique. Our study lends support to the hypothesis that extraocular muscles may influence refractive error.

Visual Acuity and Ophthalmic Outcomes 5 Years After Cataract Surgery Among Children Younger Than 13 Years.

IMPORTANCE: Cataract is an important cause of visual impairment in children. Data from a large pediatric cataract surgery registry can provide real-world estimates of visual outcomes and the 5-year cumulative incidence of adverse events. OBJECTIVE: To assess visual acuity (VA), incidence of complications and additional eye operations, and refractive error outcomes 5 years after pediatric lensectomy among children younger than 13 years. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the Pediatric Eye Disease Investigator Group clinical research registry. From June 2012 to July 2015, 61 eye care practices in the US, Canada, and the UK enrolled children from birth to less than 13 years of age who had undergone lensectomy for any reason during the preceding 45 days. Data were collected from medical record reviews annually thereafter for 5 years until September 28, 2020. EXPOSURES: Lensectomy with or without implantation of an intraocular lens (IOL). MAIN OUTCOMES AND MEASURES: Best-corrected VA and refractive error were measured from 4 to 6 years after the initial lensectomy. Cox proportional hazards regression was used to assess the 5-year incidence of glaucoma or glaucoma suspect and additional eye operations. Factors were evaluated separately for unilateral and bilateral aphakia and pseudophakia. RESULTS: A total of 994 children (1268 eyes) undergoing bilateral or unilateral lensectomy were included (504 [51%] male; median age, 3.6 years; range, 2 weeks to 12.9 years). Five years after the initial lensectomy, the median VA among 701 eyes with available VA data (55%) was 20/63 (range, 20/40 to 20/100) in 182 of 316 bilateral aphakic eyes (58%), 20/32 (range, 20/25 to 20/50) in 209 of 386 bilateral pseudophakic eyes (54%), 20/200 (range, 20/50 to 20/618) in 124 of 202 unilateral aphakic eyes (61%), and 20/65 (range, 20/32 to 20/230) in 186 of 364 unilateral pseudophakic eyes (51%). The 5-year cumulative incidence of glaucoma or glaucoma suspect was 46% (95% CI, 28%-59%) in participants with bilateral aphakia, 7% (95% CI, 1%-12%) in those with bilateral pseudophakia, 25% (95% CI, 15%-34%) in those with unilateral aphakia, and 17% (95% CI, 5%-28%) in those with unilateral pseudophakia. The most common additional eye surgery was clearing the visual axis, with a 5-year cumulative incidence of 13% (95% CI, 8%-17%) in participants with bilateral aphakia, 33% (95% CI, 26%-39%) in those with bilateral pseudophakia, 11% (95% CI, 6%-15%) in those with unilateral aphakia, and 34% (95% CI, 28%-39%) in those with unilateral pseudophakia. The median 5-year change in spherical equivalent refractive error was -8.38 D (IQR, -11.38 D to -2.75 D) among 89 bilateral aphakic eyes, -1.63 D (IQR, -3.13 D to -0.25 D) among 130 bilateral pseudophakic eyes, -10.75 D (IQR, -20.50 D to -4.50 D) among 43 unilateral aphakic eyes, and -1.94 D (IQR, -3.25 D to -0.69 D) among 112 unilateral pseudophakic eyes. CONCLUSIONS AND RELEVANCE: In this cohort study, development of glaucoma or glaucoma suspect was common in children 5 years after lensectomy. Myopic shift was modest during the 5 years after placement of an intraocular lens, which should be factored into implant power selection. These results support frequent monitoring after pediatric cataract surgery to detect glaucoma, visual axis obscuration causing reduced vision, and refractive error.

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

Purpose: Mutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM. Methods: Seven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM. Results: Foveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports. Conclusions: Our data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM.

Long-term outcomes for pediatric patients having transscleral fixation of the capsular bag with intraocular lens for ectopia lentis.

PURPOSE: To report the long-term outcomes of transscleral fixation of capsular tension rings (CTR) with intraocular lens (IOL) placement in pediatric patients with ectopia lentis. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Retrospective case series. METHODS: Pediatric patients requiring lens extraction with transscleral capsular bag fixation with a CTR and IOL for ectopia lentis between January 2006 and January 2016 were analyzed. RESULTS: Thirty-seven patients (67 eyes) who had transscleral fixation of the capsular bag using a CTR fixated with 9-0 or 10-0 polypropylene (Prolene), 8-0 polytetrafluoroethylene (Gore-Tex), or 9-0 nylon were identified. The mean age at time of surgery was 7.25 years (2 to 18 years) and the mean follow-up was 35.3 months (0.25 to 120 months). The proportion of eyes showing improvement in corrected distance visual acuity (CDVA) postoperatively was 78.5%, which demonstrated significance with a 95% confidence interval. In the immediate postoperative period, 1 eye developed a hyphema and 1 eye required IOL repositioning. Long-term complications included posterior capsule opacification in 35 eyes (52%) and uveitis-glaucoma-hyphema syndrome in 1 eye (1.5%). Three eyes (4.4 %) required IOL repositioning for spontaneous delayed IOL dislocation, 2 sutured with 8-0 polytetrafluoroethylene at postoperative month 8 and postoperative year 3 and 1 sutured with 9-0 polypropylene at postoperative year 7. CONCLUSION: Transscleral fixation of the capsular bag using a CTR improved CDVA and provided IOL stability in pediatric patients with ectopia lentis.

ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement.

PURPOSE: Photoreceptor degeneration (PRD) is a genetically heterogeneous retinal disorder. Although a number of genes involved in PRD have been identified, their genetic basis remains unknown in a significant number of patients. In this study, we aimed to identify novel disease-causing genes of PRD. METHODS: Comprehensive ocular examinations were performed in a 2-year-old patient diagnosed with early onset PRD. Retinal capture sequencing was performed to screen causative mutations in known retinal disease-causing loci. Whole-exome sequencing (WES) and a series of variant-filtering strategies were applied for identifying novel disease-causing genes. Retina ATF6 expression was confirmed by immunohistochemistry. RT-PCR was performed to identify ATF6 mRNA in the patient. RESULTS: The patient showed typical PRD features, with macular involvement and ellipsoid zone irregularities. Results of retinal capture sequencing were negative. WES data led to identification of biallelic loss-of-function mutations in the ATF6 gene. The first variant generates a premature stop codon (NCBI accession no. NM_007348: c.1126C>T, p.R376*) and the second variant affects a splicing donor site (NM_007348: c.1533+1G>C). Sanger sequencing confirmed the 2 alleles are from 1 parent each. Both of the variants are extremely rare in the population. The splicing variant causes either intron inclusion or exon skipping in the patient, thus severely disrupting ATF6 functional domains. ATF6 is expressed in three neuronal cell layers of mouse retina. CONCLUSIONS: Our results support ATF6 as a novel disease-causing gene for PRD and suggest that disrupted protein quality control mechanisms may be a novel pathological mechanism underlying human retinal degeneration.

Structural Abnormalities of the Inner Macula in Incontinentia Pigmenti.

IMPORTANCE: This report presents evidence from spectral-domain optical coherence tomography and fluorescein angiography of inner foveal structural abnormalities associated with vision loss in incontinentia pigmenti (IP). OBSERVATIONS: Two children had reduced visual behavior in association with abnormalities of the inner foveal layers on spectral-domain optical coherence tomography. Fluorescein angiography showed filling defects in retinal and choroidal circulations and irregularities of the foveal avascular zones. The foveal to parafoveal ratios were greater than 0.57 in 6 eyes of 3 patients who had extraretinal neovascularization and/or peripheral avascular retina on fluorescein angiography and were treated with laser. Of these, 3 eyes of 2 patients had irregularities in foveal avascular zones and poor vision. CONCLUSIONS AND RELEVANCE: Besides traction retinal detachment, vision loss in IP can occur with abnormalities of the inner foveal structure seen on spectral-domain optical coherence tomography, consistent with prior descriptions of foveal hypoplasia. The evolution of abnormalities in the neural and vascular retina suggests a vascular cause of the foveal structural changes. More study is needed to determine any potential benefit of the foveal to parafoveal ratio in children with IP. Even with marked foveal structural abnormalities, vision can be preserved in some patients with IP with vigilant surveillance in the early years of life.

Ophthalmologic findings in an 18-month-old boy with focal dermal hypoplasia.

Focal dermal hypoplasia is a rare X-linked dominant disorder with in utero lethality in males. Affected patients have been reported to have several different mutations in the PORCN gene on chromosome Xp11.23. Dysplastic mesodermal and ectodermal tissue causes clinical findings in the skin, skeleton, teeth, central nervous system, and eyes of affected patients. We describe the ophthalmologic findings in an 18-month-old boy with mosaicism of a novel mutation in PORCN.

Relationship between the timing of cataract surgery and development of nystagmus in patients with bilateral infantile cataracts.

PURPOSE: To study the relationship between timing of surgery as a risk factor for the development of manifest nystagmus in patients with bilateral infantile cataracts and to determine the effect of nystagmus on visual outcomes. METHODS: The medical records of patients with bilateral infantile cataracts operated on before 12 months of age between January 1991 and December 2009 were retrospectively reviewed. Patients were stratified into two groups: early (age <8 weeks) or late (age >8 weeks) surgery. RESULTS: A total of 56 patients (29 males) were studied. Early surgery was performed in 26 patients. Of these, 10 (38%) had manifest nystagmus at the most recent follow-up. Of 30 patients who underwent late surgery, 15 (50%) had manifest nystagmus at the most recent follow-up. There was not a statistically significant impact on the timing of cataract surgery and the development of postoperative nystagmus (P = 0.43). In total, 25 of 56 (45%) patients had postoperative manifest nystagmus; in these patients, there was a statistically significant decrement in final logMAR visual outcomes compared with those patients without postoperative nystagmus (0.26 vs 0.16; P = 0.04); however, preoperative nystagmus did not appear to be a risk factor for a worse visual outcome. CONCLUSIONS: Manifest nystagmus is a common feature in children with bilateral infantile cataracts, regardless of the timing of surgery. Early surgery as defined in this study does not necessarily prevent its development. Postoperative nystagmus is more common when surgery is performed later but can improve as the child matures.