Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial.

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia. Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022. Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years. Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D). Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year. Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

The association between attention-deficit/hyperactivity disorder and retinal nerve fiber/ganglion cell layer thickness measured by optical coherence tomography: a systematic review and meta-analysis.

PURPOSE: Retinal nerve fiber/ganglion cell layer (RNFL/GCL) thickness measured using optical coherence tomography has been proposed as an ocular biomarker for children with attention-deficit/hyperactivity disorder (ADHD), but findings varied in different studies. This study aims to determine the association between RNFL/GCL thickness and ADHD in children by systematic review and meta-analysis. METHODS: We performed a literature search in Embase, PubMed, Medline, Web of Science, and PsycINFO for relevant articles published up to February 29, 2020. All studies with original data comparing RNFL/GCL thickness in ADHD and healthy children were included. The Newcastle Ottawa Scale was used to assess bias risk and quality of evidence. Pooled estimates of the differences in thickness of RNFL or GCL between ADHD and healthy subjects were generated using meta-analysis with a random-effect model due to significant inter-study heterogeneity. Sensitivity analysis was also performed. RESULTS: We identified four eligible studies involving a total of 164 ADHD and 150 control subjects. Meta-analysis revealed that ADHD in children was associated with a reduction in global RNFL thickness (SMD, - 0.23; 95% CI - 0.46, - 0.01; p = 0.04). The global GCL thickness was examined in two studies with 89 ADHD and 75 control subjects, but the pooled difference in global GCL thickness between ADHD children and controls was not statistically significant (SMD, - 0.34; 95% CI - 1.25, 0.58; p = 0.47). CONCLUSION: Existing evidence suggests a possible association between ADHD and RNFL thinning in children. In view of the limited number of reports, further studies in large cohorts should be warranted.

Trends in the incidence of retinopathy of prematurity over a 10-year period.

AIM: To describe and evaluate the trends in the incidence of retinopathy of prematurity over a 10-year period in a tertiary hospital in Hong Kong. METHODS: A retrospective review was performed on all preterm infants screened and/or treated for retinopathy of prematurity from January 2006 to December 2015 at Prince of Wales Hospital, Hong Kong. Preterm infants with incomplete records or transferred-in from other hospitals/region solely for treatment of ROP were excluded. The incidence of any ROP or Type 1 ROP was analysed with gestational age and birth weight over a 10-year period with consecutive 2-year intervals to evaluate the trends. RESULTS: Of all 754 infants included in the study, 234 (31.0%) patients had any ROP and 34 (4.5%) infants developed Type 1 ROP. The incidence of any ROP demonstrated a statistically significant decreasing trend over the five consecutive 2-year intervals (p = 0.016), but the incidence trend of Type 1 ROP is not statistically significant. No infants weighing more than 1250 g developed Type 1 ROP. CONCLUSION: We observed a decreasing trend in the incidence of any ROP across the 10-year period in a tertiary hospital in Hong Kong, while the incidence of Type 1 ROP remained stable at 4.5%. The factors leading to the trend were unclear. Improved prenatal care, changing proportion of cases with different birth weight and gestational age, oxygenation level practice in neonatal unit may all contribute to the decreasing trend. Revision of screening criteria may be made according to local experience to maximise cost-effectiveness.

Visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year retrospective review in a tertiary centre in Hong Kong.

PURPOSE: To report the visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year review in Hong Kong DESIGN: Retrospective case series METHODOLOGY: Clinical records of all infants suffered from Type 1 ROP who had undergone laser therapy between 2007 and 2012 were retrospectively reviewed. Basic demographic data, serial changes of refractive error, visual acuity, severity of ROP and laser were analyzed. Correlation with myopia and astigmatism progression, body weight, height, growth and gestational age were also analyzed. RESULT: Among 494 babies screened, 14 Chinese babies (26 eyes) recruited with 1:1 male-to-female ratio in this study. All eyes showed gradual progression of myopia in first 3 years of age but no significant change of astigmatism. Further correlation analysis showed no correlation with laser energy consumed, birth weight (p = 0.14), head circumference growth (p = 0.57) and body weight growth (p = 0.71). However, severity of myopia was related to the post-conceptual age when receiving laser therapy (p < 0.005), gestation age (p = 0.02) and possibly body height growth with age (p = 0.05). CONCLUSION: Myopia in early life is one of the most common ocular sequelae in Type 1 ROP survivors. Early detection of refractive error is important for prompt correction and visual rehabilitation to prevent amblyopia.

Etiologies and surgical outcomes of pediatric retinal detachment in Hong Kong.

The purpose of this study was to study the etiologies and operative outcomes of pediatric retinal detachment at a tertiary eye referral center in Hong Kong over a 10-year period. A retrospective study of patients (below 18 years of age) who received primary retinal detachment repair operations at a University Teaching Hospital between 2005 and 2015 was conducted. The study comprised 37 patients with 39 eyes affected who received primary retinal detachment (RD) surgery. Two patients had bilateral RD. 69.2 % were male. The mean follow-up period was 40.6 ± 28.6 months. Their mean age at presentation was 13.4 ± 5.5 years. There were contributing factors for RD identified in 33 eyes (84.6 %), of which congenital/developmental anomalies (23.1 %), high myopia with refractive error greater than -6 diopters (17.9 %), and trauma (15.4 %) ranked the top 3 causes for RD. The retina was reattached after one surgical procedure in 69.2 %. Final anatomical success rate was 82.1 %. Postoperatively, 68.8 % of eyes had improved or stable vision. Functional visual loss with visual acuity less than 5/200 was found to be 30.6 % of eyes which were mostly from younger patients and those with congenital anomalies. Pediatric retinal detachment is often associated with predisposing factors. The presence of congenital/developmental ocular anomalies causing retinal detachment is more frequent in younger children and with worse functional and visual outcomes. Continuing efforts to improve treatment strategies for this group of patients are needed.

Three different ophthalmic presentations of juvenile xanthogranuloma.

Three cases of juvenile xanthogranuloma from two ophthalmology departments were reviewed. Clinical histories, ophthalmic examination, physical examination, investigations, and treatment of these cases are described. A 4-month-old boy presented with spontaneous hyphema and secondary glaucoma. He was treated with intensive topical steroid and anti-glaucomatous eye drops. The hyphema gradually resolved and the intra-ocular pressure reverted to 11 mm Hg without any other medication. Biopsy of his scalp mass confirmed the diagnosis of juvenile xanthogranuloma. A 31-month-old boy presented with a limbal mass. Excisional biopsy of the mass was performed and confirmed it was a juvenile xanthogranuloma. A 20-month-old boy was regularly followed up for epiblepharon and astigmatism. He presented to a paediatrician with a skin nodule over his back. Skin biopsy confirmed juvenile xanthogranuloma. He had no other ocular signs. Presentation of juvenile xanthogranuloma can be very different, about which ophthalmologists should be aware of. Biopsy of the suspected lesion is essential to confirm the diagnosis.

Diversified clinical presentations associated with a novel sal-like 4 gene mutation in a Chinese pedigree with Duane retraction syndrome.

PURPOSE: To determine the underlying genetic cause of Duane retraction syndrome (DRS) in a non-consanguineous Chinese Han family. METHODS: Detailed ophthalmic and physical examinations were performed on all members from a pedigree with DRS. All exons and their adjacent splicing junctions of the sal-like 4 (SALL4) gene were amplified with polymerase chain reaction and analyzed with direct sequencing in all the recruited family members and 200 unrelated control subjects. RESULTS: Clinical examination revealed a broad spectrum of phenotypes in the DRS family. Mutation analysis of SALL4 identified a novel heterozygous duplication mutation, c.1919dupT, which was completely cosegregated with the disease in the family and absent in controls. This mutation was predicted to cause a frameshift, introducing a premature stop codon, when translated, resulting in a truncated SALL4 protein, i.e., p.Met640IlefsX25. Bioinformatics analysis showed that the affected region of SALL4 shared a highly conserved sequence across different species. Diversified clinical manifestations were observed in the c.1919dupT carriers of the family. CONCLUSIONS: We identified a novel truncating mutation in the SALL4 gene that leads to diversified clinical features of DRS in a Chinese family. This mutation is predicted to result in a truncated SALL4 protein affecting two functional domains and cause disease development due to haploinsufficiency through nonsense-mediated mRNA decay.

Efficacy and Safety of 6-Weekly versus 12-Weekly Intravenous Methylprednisolone in Moderate-to-Severe Active Thyroid-Associated Ophthalmopathy.

PURPOSE: To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. BASIC PROCEDURES: Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. MAIN FINDINGS: A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25-74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves' disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/-ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups.

Association of Polymorphisms in ZFHX1B and PAX6 With Anisometropia in Chinese Children: The Hong Kong Children Eye Genetics Study.

Purpose: To identify gene variants associated with anisometropia development in children. Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children. Anisometropia was defined by an interocular difference in SE of ≥1 diopter (D) (Aniso-SE) and an interocular difference in axial length (AL) of ≥0.3 mm (Aniso-AL), respectively. Genetic associations of individual SNPs and joint SNP effects were analyzed. Results: ZFHX1B rs13382811 was associated nominally with Aniso-AL (odds ratio [OR], 1.66; P = 0.003) at baseline. At 3 years, rs13382811 was significantly associated with Aniso-AL (OR, 1.49; P = 0.001) and became nominally associated with Aniso-SE (OR, 1.40; P = 0.01). In addition, PAX6 rs644242 was significantly associated with Aniso-AL at 3 years (OR, 1.45; P = 0.002). At the 3-year follow-up, PAX6 rs644242 was associated significantly with Aniso-AL development (OR, 1.61; P = 0.0003) and nominally with Aniso-SE development (P = 0.03) in children who were not anisometropic at baseline, whereas ZFHX1B rs13382811 was associated nominally with Aniso-AL development (P = 0.02). An additive SNP analysis indicated children carrying the risk allele T of ZFHX1B rs13382811 and allele A of PAX6 rs644242 might have a 4.33- and 6.90-fold of increased risk of Aniso-SE and Aniso-AL development by 3 years, respectively. Conclusions: This study identified two susceptible gene variants, ZFHX1B rs13382811 and PAX6 rs644242, for anisometropia development in Hong Kong Chinese children, implicating their role in imbalanced refractive change and axial elongation between both eyes.

Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation.

PURPOSE: To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance. METHODS: Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric-phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained. RESULTS: Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost. CONCLUSIONS: Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.

Developing a privacy-preserving deep learning model for glaucoma detection: a multicentre study with federated learning.

BACKGROUND: Deep learning (DL) is promising to detect glaucoma. However, patients' privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images. METHODS: This is a multicentre study. The FL paradigm consisted of a 'central server' and seven eye centres in Hong Kong, the USA and Singapore. Each centre first trained a model locally with its own OCT optic disc volumetric dataset and then uploaded its model parameters to the central server. The central server used FedProx algorithm to aggregate all centres' model parameters. Subsequently, the aggregated parameters are redistributed to each centre for its local model optimisation. We experimented with three three-dimensional (3D) networks to evaluate the stabilities of the FL paradigm. Lastly, we tested the FL model on two prospectively collected unseen datasets. RESULTS: We used 9326 volumetric OCT scans from 2785 subjects. The FL model performed consistently well with different networks in 7 centres (accuracies 78.3%-98.5%, 75.9%-97.0%, and 78.3%-97.5%, respectively) and stably in the 2 unseen datasets (accuracies 84.8%-87.7%, 81.3%-84.8%, and 86.0%-87.8%, respectively). The FL model achieved non-inferior performance in classifying glaucoma compared with the traditional model and significantly outperformed the individual models. CONCLUSION: The 3D FL model could leverage all the datasets and achieve generalisable performance, without data exchange across centres. This study demonstrated an OCT-based FL paradigm for glaucoma identification with ensured patient privacy and data security, charting another course toward the real-world transition of artificial intelligence in ophthalmology.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study.

BACKGROUND: Oral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored. STUDY POPULATION: A city-wide, biopsy-proven, Chinese cohort. METHODS: Retrospective, masked review of medical records, orbital images and histopathology reports. RESULTS: There were 101 patients with at least 24-month follow-up. Up to 82% (82/101) received oral corticosteroid as first-line treatments, and 7 of them received also concomitant steroid-sparing agents (SSA)/biological agents as primary treatment. There was 61% (50/82) of patients required long-term corticosteroid (alone=23, with SSA=27) after 1.9±0.7 (range 1-5) relapses. When compared with the 21% (17/82) of patients who tapered corticosteroid successfully for 24 months, steroid dependence was associated with elevated baseline serum IgG4 level (94% vs 65%, p<0.01) and Mikulicz syndrome (46% vs 18%, p<0.05). Up to 13% (11/82) of patients tolerated residual disease after tapering off corticosteroid. There was 17% (17/101) of patients did not require any medications after biopsies. They were more likely to have debulking surgeries (71% vs 40%, p<0.05), discrete orbital lesions (65% vs 26%, p<0.05), normal baseline serum IgG4 level (24% vs 6%, p<0.05) and no Mikulicz syndrome (94% vs 61%, p<0.05). CONCLUSION: In this cohort, 60% of patients required long-term maintenance oral corticosteroid. Elevated pretreatment serum IgG4 level and Mikulicz syndrome were associated with steroid dependence. Debulking surgery is an alternative for a subgroup of patients with discrete orbital lesions, normal baseline IgG4 level and no Mikulicz syndrome.

Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.

Radiological Determinants of Complicated Immunoglobulin G4-Related Ophthalmic Disease: A Territory-Wide Cohort Study.

PURPOSE: To evaluate the presenting radiological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and their associations with IgG4-related optic neuropathy (IgG4-RON), and IgG4-related ocular adnexal lymphoma (IgG4-ROL). METHODS: A territory-wide, biopsy-proven, Chinese cohort. Masked review of orbital images, medical records, and histopathology reports. RESULTS: A total of 115 (94%) of the 122 patients in our cohort had preoperative orbital images (computed tomography=105, magnetic resonance imaging=40). Among them, 103/115 (90%) showed enlarged lacrimal glands, and 91 (88%) were bilateral. Nerve enlargement was observed: infraorbital in 31/115 (27%) patients and frontal in 17/115 (15%), 10 and 9 being bilateral, respectively. At least 1 or more extraocular muscle (EOM) enlargement was found in 41/115 (37%) patients, bilaterally in 20. Lateral rectus occurred in 30 (73%) of these 41 EOM patients and inferior rectus in 28 (68%). Two adjacent EOMs (inferior and lateral recti in 11 patients, inferior and medial recti in 7 patients) or multiple EOMs (at least 3) were enlarged in 23/41 (56%) and 13/41 (32%) of the patients, respectively. Intraconal lesions (67% vs 11%, P<0.05), infraorbital (83% vs 23%, P<0.005), or frontal (50% vs 15%, P<0.05) nerve enlargement was significantly associated with IgG4-RON (6 patients) by univariate analyses. Asymmetric lacrimal gland enlargement and discrete orbital mass (both P<0.05) were associated with IgG4-ROL (9 patients) by multivariate analyses. CONCLUSIONS: In this IgG4-ROD cohort, most patients had bilateral enlarged lacrimal glands, and the lateral rectus is the most frequently involved EOM. For the first time, unique radiological patterns associated with the development of IgG4-RON and IgG4-ROL are found.

Genetic associations of myopia severities and endophenotypes in children.

OBJECTIVE: To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children. METHODS: A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed. RESULTS: When compared with controls, SNPs ZC3H11B rs4373767 (OR=1.15, p=0.038), BICC1 rs7084402 (OR=1.18, p=0.005) and GJD2 rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. ZC3H11B rs4373767 and BICC1 rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while GJD2 rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). GJD2 rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, ZC3H11B rs4373767, KCNQ5 rs7744813 and GJD2 rs524952 were correlated with both myopic SE (ß=-0.09, p=0.03; ß=-0.12, p=0.007; ß=-0.13, p=0.0006, respectively) and AL (ß=0.07, p=0.002; ß=0.09, p=0.0008; ß=0.07, p=0.0003, respectively). SNTB1 rs7839488 was correlated with both AL (ß=0.07, p=0.005) and CR (ß=0.02, p=0.006). Moreover, ZC3H11B rs4373767-T (ß=0.006; p=0.018), KCNQ5 rs7744813-A (ß=0.007; p=0.015) and GJD2 rs524952-T (ß=0.009; p=0.0006) were correlated with AL-CR ratio. CONCLUSIONS AND RELEVANCE: ZC3H11B and BICC1 are genetic risk factors for moderate and high myopia, while ZC3H11B, KCNQ5, SNTB1 and GJD2 confer risk to excessive AL in children.

Association of WNT7B and RSPO1 with Axial Length in School Children.

Purpose: To evaluate the association between single-nucleotide polymorphisms (SNPs) in the ZC3H11B, RSPO1, C3orf26, GJD2, ZNRF3, and WNT7B genes and myopia endophenotypes in children. Methods: Seven SNPs identified in previous genome-wide association studies of axial length (AL) were genotyped in 2883 Southern Han Chinese children. Multiple linear regression analyses were conducted to evaluate the genotype association with AL, spherical equivalent (SE), corneal curvature (CC), and central corneal thickness (CCT). Results: Two SNPs-namely, rs12144790 in RSPO1 (allele T, P = 0.0066, ß = 0.062) and rs10453441 in WNT7B (allele A, P = 8.03 × 10-6, ß = 0.103)-were significantly associated with AL. The association of rs4373767 in ZC3H11B (allele C, P = 0.030, ß = -0.053) could not withstand the correction for multiple testing. WNT7B rs10453441 showed a strong association with CC (P = 1.17 × 10-14, ß = 0.053) and with CCT (P = 0.0026, ß = 2.65). None of the tested SNPs was significantly associated with SE. The C allele of SNP rs12321 in ZNRF3 was associated with CC (P = 0.0060, ß = -0.018). Conclusions: This study revealed that the RSPO1 SNP rs12144790 was associated with AL, whereas WNT7B rs10453441 was associated with AL, CC, and CCT in children. A novel association between ZNRF3 rs12321 and CC was discovered. Our data suggest that the RSPO1 and WNT7B genes might exert their effects on multiple aspects of eye growth during childhood. Potential differences in the genetic profiles of AL between children and adults should be explored in larger cohorts.

Serous retinal detachment in Joubert syndrome.

This report describes a 3-year-old Chinese-Italian boy with Joubert syndrome. Fundus examination showed bilateral optic disc coloboma. Left serous retinal detachment was also found. This ocular finding was not reported in the previous literature. Although Joubert syndrome has many variable phenotypes and the molecular basis is still unknown, the newly reported ocular features suggest that a different genetic form may be present.

Anterior segment ischemia after two-muscle surgery in a patient with radiation-treated nasopharyngeal carcinoma.

Anterior segment ischemia after strabismus surgery is a rare occurrence. Risk factors include single-stage surgery of three or more muscles in one eye, dysthyroid eye disease, and advanced age. The authors report a case of anterior segment ischemia after single-stage surgery of two horizontal muscles without previous reported risk factors. However, the patient had received radiotherapy for nasopharyngeal carcinoma more than 20 years ago. The case was successfully treated with systemic steroids but with reduced best-corrected visual acuity. Previous radiotherapy in the related orbital field may be a new risk factor for this condition.