Filaggrin-Associated Atopic Skin, Eye, Airways, and Gut Disease, Modifying the Presentation of X-Linked Reticular Pigmentary Disorder (XLPDR).

BACKGROUND: X-linked reticular pigmentary disorder (XLPDR) is a rare condition characterized by skin hyperpigmentation, ectodermal features, multiorgan inflammation, and recurrent infections. All probands identified to date share the same intronic hemizygous POLA1 hypomorphic variant (NM_001330360.2(POLA1):c.1393-354A > G) on the X chromosome. Previous studies have supported excessive type 1 interferon (IFN) inflammation and natural killer (NK) cell dysfunction in disease pathogenesis. Common null polymorphisms in filaggrin (FLG) gene underlie ichthyosis vulgaris and atopic predisposition. CASE: A 9-year-old boy born to non-consanguineous parents developed eczema with reticular skin hyperpigmentation in early infancy. He suffered recurrent chest infections with chronic cough, clubbing, and asthma, moderate allergic rhinoconjunctivitis with keratitis, multiple food allergies, and vomiting with growth failure. Imaging demonstrated bronchiectasis, while gastroscopy identified chronic eosinophilic gastroduodenitis. Interestingly, growth failure and bronchiectasis improved over time without specific treatment. METHODS: Whole-genome sequencing (WGS) using Illumina short-read sequencing was followed by both manual and orthogonal automated bioinformatic analyses for single-nucleotide variants, small insertions/deletions (indels), and larger copy number variations. NK cell cytotoxic function was assessed using 51Cr release and degranulation assays. The presence of an interferon signature was investigated using a panel of six interferon-stimulated genes (ISGs) by QPCR. RESULTS: WGS identified a de novo hemizygous intronic variant in POLA1 (NM_001330360.2(POLA1):c.1393-354A > G) giving a diagnosis of XLPDR, as well as a heterozygous nonsense FLG variant (NM_002016.2(FLG):c.441del, NP_0020.1:p.(Arg151Glyfs*43)). Compared to healthy controls, the IFN signature was elevated although the degree moderated over time with the improvement in his chest disease. NK cell functional studies showed normal cytotoxicity and degranulation. CONCLUSION: This patient had multiple atopic manifestations affecting eye, skin, chest, and gut, complicating the presentation of XLPDR. This highlights that common FLG polymorphisms should always be considered when assessing genotype-phenotype correlations of other genetic variation in patients with atopic symptoms. Additionally, while the patient exhibited an enhanced IFN signature, he does not have an NK cell defect, suggesting this may not be a constant feature of XLPDR.

Integration of hospital and community care for paediatric ophthalmology: A mixed-methods study.

BACKGROUND: To explore collaborative care models for paediatric eye care that integrate hospital and community-based care to address access blocks. METHODS: Sequential referrals to a tertiary paediatric ophthalmology clinic between April and October 2019 and subsequent encounters up until July 2020 at a major metropolitan public children's hospital in Sydney, Australia, were reviewed to identify those cases suitable for community care. Semi-structured phone interviews were conducted with eye health service providers, including ophthalmologists, orthoptists and optometrists, as well as service users to explore their perspectives on potential changes to service delivery. Qualitative data were analysed deductively using the Levesque model for access to healthcare and Consolidated Framework for Implementation Research (CFIR) to inform implementation strategies for future models of care. RESULTS: One-third of the 439 audited referrals (30.5%; 134/439) were identified as suitable for community management. Interviews revealed five themes relating to potential models of care, which would support and promote access: integrated health systems, standardised quality of care, interprofessional trust, multidisciplinary governance and patient-centred care. Key recommendations for future implementation included: (i) identifying and preparing clinical champions, (ii) conducting educational meetings, (iii) conducting local needs assessments and (iv) informing local opinion leaders. CONCLUSIONS: This audit highlights access blocks and poor targeting of referrals to tertiary paediatric ophthalmology services in a metropolitan hospital. Integration with community practitioners was identified as an acceptable way to streamline services, and strategies that may support successful implementation in this setting were identified.

Rising trends of endogenous Klebsiella pneumoniae endophthalmitis in Australia.

BACKGROUND: Endogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well-known entity in South-East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia. DESIGN: Retrospective observational case study and case series in the hospital setting. PARTICIPANTS: Four cases of EKPE. METHODS: EKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital-based microbiological searches. MAIN OUTCOME MEASURES: EKPE cases were confirmed with positive K. pneumoniae intraocular samples. RESULTS: Rising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43-58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better. CONCLUSIONS: EKPE is an emerging condition in Australia. Although rare, EKPE is a sight-threatening and potentially life-threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B-scan showing a vitreous or retinal abscess.

Corneal Collagen Cross-linking for Keratoconus in Pediatric and Developmentally Delayed Patients.

PURPOSE: Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups. METHODS: A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA). RESULTS: Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively (P = 0.3) in DD and 0.52 and 0.36, respectively (P = 0.13), in NDD. CONCLUSIONS: This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain.

Technique for the Management of Extensive Ocular Surface Lipodermoid Involving the Cornea of Children.

PURPOSE: Ocular surface lipodermoids with corneal involvement may require surgical intervention; if deep, ocular surface reconstruction with lamellar corneal tissue or amniotic membrane may be needed. We describe a staged technique using autologous ipsilateral simple limbal epithelial transplantation. METHODS: After verifying sparing of Descemet membrane, the conjunctival portion of the lipodermoid was debulked in the first stage. Six weeks later, the corneal portion was excised, followed by autologous ipsilateral simple limbal epithelial transplantation to promote rapid reepithelialization of the residual stromal bed. Temporary tarsorrhaphy was used for patient comfort and to expedite ocular surface healing. RESULTS: Three eyes of 3 children with grade III large ocular surface lipodermoids that encroached the visual axis and hindered proper eyelid closure underwent surgery without complications. In all cases, the visual axis was cleared and eyelid closure was improved. At the last follow-up (mean 35.7 months, median 36.0 months), the bed of the original dermoid showed minimal haze in 1 case, while 2 eyes developed small pseudopterygium; best spectacle-corrected visual acuity improved from 20/200 to 20/70 in the first case, from fix and follow to 20/50 in the second case, and remained fix and follow in the last case, but this child had congenital hydrocephalus with severe developmental delay. CONCLUSIONS: This surgical technique is a promising option for children with grade III large ocular surface lipodermoids given its effectiveness in clearing the visual axis and in improving eyelid closure. Moreover, it does not require lamellar corneal transplantation or intervention to the fellow eye.

Congenital Corneal Opacity in 22q11.2 Deletion Syndrome: A Case Series.

PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

Ocular Phenotype of Peters-Plus Syndrome.

PURPOSE: Peters-plus syndrome is a rare, autosomal recessive congenital disorder of glycosylation caused by mutations in the gene B3GLCT. A detailed description of the ocular findings is currently lacking in the scientific literature. We report a case series of Peters-plus syndrome with deep ocular phenotyping using anterior segment optical coherence tomography and ultrasound biomicroscopy. Where available, we describe the histology of host corneal buttons. METHODS: A retrospective chart review of patients with Peters-plus syndrome was conducted under the care of the senior author between January 2000 and June 2019. Demographic and clinical data including ocular and systemic features, ophthalmic imaging, and molecular diagnostic reports were collected. RESULTS: Four cases of Peters-plus syndrome were identified. Three patients were male and 1 was female. Five of the 8 eyes had an avascular paracentral ring opacity with relative central clearing. The paracentral opacity is due to iridocorneal adhesion and the relative central clearing associated with posterior stromal thinning. One eye had persistent fetal vasculature and microphthalmia, which has not previously been reported. One eye from each of 2 patients had a significantly different phenotype with a large vascularized central corneal opacity. CONCLUSIONS: The most common ocular phenotype seen in Peters-plus syndrome is an avascular paracentral ring opacity with relative central clearing. A different phenotype with a large vascularized corneal opacity may also be observed.

Temperature dependence of diffusiophoresis via a novel microfluidic approach.

The temperature dependence of the diffusiophoretic mobility (DDP) is investigated experimentally and compared with theoretical predictions. These systematic measurements were made possible by a new microfluidic approach that enables truly steady state gradients to be imposed, and direct and repeatable measurements of diffusiophoretic migration to be made over hours-long time scales. Diffusiophoretic mobilities were measured for fluorescent, negatively charged polystyrene particles under NaCl gradients, at temperatures ranging from 20 °C to 70 °C. Measured DDP values were found to increase monotonically with temperature, and to agree, both qualitatively and relatively quantitatively, with theoretical predictions based on electrophoretically-measured zeta potentials. These results provide confidence that existing diffusiophoresis theories can accurately predict DP mobilities over a range of temperatures. More broadly, we anticipate our new microfluidic approach will facilitate and enable new tests of diffusiophoretic phenomena under a wide range of physical and chemical conditions.

Integrated Intraoperative Optical Coherence Tomography in Strabismus Surgery.

The advent of integrated intraoperative ocular coherence tomography (i2OCT) has opened the door for safer more complex surgeries of the retina and cornea. However, to limit its use to just two subspecialties within ophthalmology is an opportunity lost for many other subspecialties. Here, we describe the use of i2OCT in strabismus surgery. It can be used to identify extraocular muscles, especially in cases of strabismus reoperations, thereby augmenting the surgical technique. Its use to help train strabismus surgery is invaluable, allowing the trainee to understand the depth of the scleral pass during strabismus surgery. The authors describe these scenarios of training and augmenting the surgical technique.

Comparison of Subjective and Objective Torsion in Normal Patients.

PURPOSE: To compare subjective and objective torsion in normal individuals. METHODS: A total of 59 individuals (118 eyes) were recruited from one ophthalmology institute in New South Wales, Australia. Objective torsion was measured with optical coherence tomography (OCT) (Heidelberg Engineering) and subjective torsion measurements were obtained with the Torsionometer (INNOVA). RESULTS: Kendall's tau correlation coefficient when comparing the Torsionometer to combined left and right OCT measurements was 0.115 (95% CI: -0.085 to 0.322), inferring a weak correlation. Similarly, when the Torsionometer readings were compared with the OCT measurements of each eye separately, the results demonstrated a weak correlation. CONCLUSIONS: To the authors' knowledge, this is the first study comparing subjective and objective torsion in normal individuals. The results demonstrate that subjective and objective torsion in normal individuals should be considered as separate entities and the terms should not be used interchangeably. [J Pediatr Ophthalmol Strabismus. 2021;58(2):112-117.].

Analysis of the impact of COVID-19 pandemic on house-staff in the USA: addressing the ripple effects.

Background: The novel corona virus has changed the way individuals interact with each other and society. In the medical sector, this has affected the residents and fellows who spend the majority of their time on the front lines. Methods: We conducted a cross-sectional survey to assess the impact of the COVID-19 pandemic on the lives and training of house-staff across the USA. Respondents in our survey reported feeling significantly overwhelmed by the ongoing pandemic. Results: The majority of house-staff were significantly concerned about the lack of protective equipment, inability to safeguard themselves from infection and inability to look after their families. Concerns regarding contracting the infection and transmitting it to their loved ones were reported as a cause of mental distress among resident physicians. Increasing patient load, lack of protective equipment, and disruption of educational and academic activities during the COVID-19 pandemic have all reportedly affected the training and overall well-being of resident physicians. Conslusion: Our study adds further support for measures to safeguard house-staff with proper protective equipment and ensure adequate support for both mental and physical well-being during these challenging times.

Transposition of plicated horizontal muscles.

Various surgical techniques exist for simultaneous correction of a strabismus with both horizontal and vertical components. Transposition of horizontal muscles is most commonly performed on recessed and resected muscles. We describe a novel surgical technique that combines horizontal rectus muscle plication with a vertical transposition and present a small case series in which the technique was used to successfully correct both horizontal and vertical deviations.

Development of Corneal Sensation With Remodeling of the Epithelium and the Palisades of Vogt After Corneal Neurotization.

PURPOSE: Neurotrophic keratopathy (NK) produces persistent epithelial erosion which is hard to treat effectively. Recently, corneal neurotization surgery has produced reinnervation of the cornea with resolving neurotrophic keratopathy. We hypothesized that the generation of corneal epithelial nerves after neurotization surgery would not only restore the integrity of corneal epithelium but also produce a change in the configuration of the palisades of Vogt (POV), which houses the corneal epithelial stem cells. METHODS: We assessed a patient with unilateral congenital corneal anesthesia with optical coherence tomography pre-neurotization and post-neurotization. RESULTS: Over the course of 2 years, the patient gained corneal epithelial sensation and corneal and limbal epithelium was restored to normal thickness with corresponding changes in the POV. CONCLUSIONS: The intimate relationship between epithelium and sensory nerves of the cornea has been well documented; however, changes in the corneal epithelial stem cell niche in conjunction with development of innervation have not previously been reported. Considering the architecture of the corneal nerves in conjunction with the architecture of the POV may assist in developing treatments that can support the regeneration and maintenance of epithelium during nerve regeneration.

Pre-, Intra-, and Post-Operative Evaluation of Extraocular Muscle Insertions Using Optical Coherence Tomography: A Comparison of Four Devices.

OCT (optical coherence tomography) is widely used in ophthalmology and pediatric ophthalmology, but limited research has been done on the use of OCT in strabismus. This study investigates the use of different OCT machines to image rectus muscle insertions pre-, intra-, and post-operatively in pediatric strabismus patients. The OCT machines used in the study were a Bioptigen (Leica Microsystems Inc., Buffalo Grove, IL, USA), Spectralis HRA+OCT with Anterior Segment Module (Heidelberg Engineering, Heidelberg, Germany), Visante (Carl Zeiss, Oberkochen, Germany), and Zeiss Rescan 700 (Carl Zeiss, Oberkochen, Germany). Measurements from the machines were compared with the caliper distance measured during the strabismus surgery before disinsertion or after reattachment. The OCT machines had moderate (Bioptigen: 0.62) to good intraclass correlation coefficients (Rescan: 0.83, Spectralis: 0.85, Visante: 0.88) with intra-operative measurements. To our knowledge, this is the first study to use an operating microscope with integrated intra-operative OCT to image rectus muscle insertions. OCT is a useful tool in strabismus surgical patients in the pre-, intra-, and post-operative settings, particularly in patients who have had previous surgery, when the muscle insertion is unknown. The ability to accurately image rectus muscle insertions has significant implications for the management of strabismus patients.

Ophthalmic Manifestations of Mycoplasma-Induced Rash and Mucositis.

PURPOSE: Mycoplasma pneumoniae is a common cause of pediatric respiratory infections, with a quarter having extrapulmonary complications, most commonly a mucocutaneous eruption involving the ocular surface. A detailed description of the ophthalmic manifestations in Mycoplasma-induced rash and mucositis (MIRM) is currently lacking in the scientific literature. METHODS: This is a retrospective chart review of consecutive cases of MIRM at a tertiary referral children's hospital between October 1 and December 1, 2018, with up to 2 months of follow-up. Main outcomes and measures were demographic information, clinical examination findings including visual acuity, detailed anterior segment findings, and course of both ophthalmic and systemic disease. RESULTS: Five patients were included. Age range was 8 to 17 years (mean age 11.9 years, median 11 years), with a strong male preponderance (4:1). All patients had inflammatory conjunctivitis. One patient had recurrent conjunctival pseudomembrane formation, whereas 2 patients had lid margin and conjunctival ulceration. No cases had corneal involvement and visual outcomes were excellent. CONCLUSIONS: MIRM is associated with ocular involvement in almost all cases. Although this is generally mild, conjunctival epithelial defects and pseudomembrane formation can occur. We recommend that pediatric ophthalmologists follow children who are hospitalized with MIRM as closely as they would those diagnosed with other mucocutaneous syndromes, such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Personalized pediatric ophthalmology: a case report.

The availability of genetic sequencing has given physicians a new tool for diagnosis and treatment of disease, and "personalized medicine" has become an increasingly common term in general but not in pediatric ophthalmology. We present a case of a toddler who developed ataxia, opsoclonus, myoclonus, and developmental regression following anesthesia for a common otolaryngology procedure. The child was found to have a variant in the MT-ND6 gene (m.14484T>C), most commonly associated with Leber hereditary optic neuropathy, despite a phenotype more closely resembling Leigh syndrome. The incongruence of phenotype and genotype prompted whole exome sequencing, which identified an unexpected intronic missense mutation in RB1 (1960+5G>A), with a 90% penetrance for retinoblastoma. Limited evaluation of the posterior pole in clinic did not identify any lesions, and the risks and benefits of examination under anesthesia were discussed among neurology, ophthalmology, and anesthesiology. We report the outcome of these discussions. The value and risks of personalized medicine are discussed.

Uveal Effusion: Clinical Features, Management, and Visual Outcomes in a Retrospective Case Series.

PURPOSE: To present the experience of a tertiary care ophthalmic institution in the assessment and management of uncommon causes of uveal effusion and related complications. MATERIALS AND METHODS: A retrospective chart review was conducted of 12 patients diagnosed with uveal effusion and managed at our institution between 1996 and 2012. The presenting features, investigations, management, and outcomes were analyzed for each case. RESULTS: The case series encompasses a variety of clinical conditions that cause uveal effusion including inflammatory, hydrostatic, and idiopathic mechanisms. Two thirds of the patients presented with secondary angle closure. Half of the patients had serous retinal detachment. Modern imaging techniques including ultrasound biomicroscopy and high-resolution magnetic resonance imaging were critical in making the diagnosis. Seven of the 12 patients responded to medical treatment and 4 required scleral surgery. Uveal effusions resolved in all patients after treatment. CONCLUSIONS: Uveal effusion is a complex and poorly understood clinical entity with significant visual morbidity and is caused by a range of ocular and systemic diseases. Effective management is critically dependent on the underlying cause.