Novel LOXL3-associated stickler syndrome-like phenotype: a case report.

PURPOSE: To report the case of a young boy with early onset high myopia (eoHM), foveal hypoplasia and skeletal dysplasia due to a homozygous LOXL3 pathogenic variant. Atypically, this was from a paternal uniparental isodisomy (UPiD) of chromosome 2. CLINICAL CASE: Four-year-old boy with several months history of holding items close to his face was found to have reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed spondylo-epi-metaphyseal dysplasia. Whole-exome sequencing (WES) revealed a homozygous LOXL3 variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2. CONCLUSION: To our knowledge, this is the first reported case of LOXL3-associated eoHM, foveal hypoplasia and mild skeletal dysplasia due to the rare phenomenon of paternal UPiD of chromosome 2. This case further delineates the phenotype associated with LOXL3 pathogenic variants and supports truncating LOXL3 pathogenic variants being associated with a phenotypic spectrum; from isolated eoHM through to a Stickler syndrome-like phenotype.

Comparison of Weight-Gain-Based Prediction Models for Retinopathy of Prematurity in an Australian Population.

Purpose: Four weight-gain-based algorithms are compared for the prediction of type 1 ROP in an Australian cohort: the weight, insulin-like growth factor, neonatal retinopathy of prematurity (WINROP) algorithm, the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOPROP), the Colorado Retinopathy of Prematurity (CO-ROP) algorithm, and the postnatal growth, retinopathy of prematurity (G-ROP) algorithm. Methods: A four-year retrospective cohort analysis of infants screened for ROP in a tertiary neonatal intensive care unit in Brisbane, Australia. The main outcome measures were sensitivities, specificities, and positive and negative predictive values. Results: 531 infants were included (mean gestational age 28 + 3). 24 infants (4.5%) developed type 1 ROP. The sensitivities, specificities, and negative predictive values, respectively, for type 1 ROP (95% confidence intervals) were for WINROP 83.3% (61.1-93.3%), 52.3% (47.8-56.7%), and 98.4% (96.1-99.4%); for CHOPROP 100% (86.2-100%), 46.0% (41.7-50,3%), and 100% (98.4-100%); for CO-ROP 100% (86.2-100%), 32.0% (28.0%-36.1%), and 100% (98.3-100%); and for G-ROP 100% (86.2-100%), 28.2% (24.5-32.3%), and 100% (97.4-100%). Of the five infants with persistent nontype 1 ROP that underwent treatment, only CO-ROP was able to successfully identify all. Conclusions: CHOPROP, CO-ROP, and G-ROP performed well in this Australian population. CHOPROP, CO-ROP, and G-ROP would reduce the number of infants requiring examinations by 43.9%, 30.5%, and 26.9%, respectively, compared to current ROP screening guidelines. Weight-gain-based algorithms would be a useful adjunct to the current ROP screening.

Increased risk of retinopathy of prematurity since increased O2 saturation targets: A multi-centre study.

BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is a leading cause of visual impairment in premature neonates. The BOOST II, SUPPORT and COT trials recommended increasing O2 saturation targets for pre-term neonates to reduce mortality; however, this is a risk factor for ROP. We aimed to determine whether these targets increased prevalence of ROP among pre-term neonates and higher risk groups. METHODS: Retrospective cohort study conducted using data from the Australian and New Zealand Neonatal Network. 17 298 neonate cohort born 2012-2018 at <32 weeks' GA and/or <1500 g BW was analysed. Adjusted odds ratios (aORs) were calculated for post-2015 risk of: any ROP; ROP ≥ Stage 2; and treated ROP. Sub-analysis stratified at <28 GA, < 26 weeks' GA, <1500 g BW and <1000 g BW was performed. RESULTS: Risk of any ROP increased in the post-2015 group (aOR = 1.23, 95% confidence interval (CI) = 1.14-1.32), <28 weeks' GA (aOR = 1.31, 95% CI = 1.17-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.24, 95% CI = 1.14-1.34) and <1000 g (aOR = 1.34, 95% CI = 1.20-1.50). ROP ≥ Stage 2 increased at <28 weeks (aOR = 1.30, 95% CI = 1.16-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.18, 95% CI = 1.08-1.30), and <1000 g (aOR = 1.26, 95% CI = 1.13-1.42). CONCLUSION: O2 therapy guidelines since 2015 have resulted in decreased mortality but increased risk of ROP. Individualised NICU adjustments of ROP screening/follow-up methods are necessary to address the clinical burden.

Validity and repeatability of contour-based visotec distance stereoacuity test.

CLINICAL RELEVANCE: The clinical assessment of distance stereoacuity is important in some ocular conditions. Given the different neurophysiological mechanism for crossed and uncrossed stereoacuities, evaluation of both may provide additional insight into binocular vision disorders. BACKGROUND: Clinical devices measuring distance crossed and uncrossed stereopsis are not readily available. Visotec Distance Stereo Test (VDST) is a contour-based device designed to measure both forms of distance stereoacuity. This study assesses the validity and test-retest reliability of the device in comparison to the random dot-based Randot Distance Stereo Test (RDST). METHOD: VDST and RDST were administered to a total of 107 children, that included 51 'normal' and 56 'abnormal' (37 intermittent exotropia and 19 amblyopia) between the ages of 5 and 15 years. Two examiners retested stereoacuities in a sub-set of 62 randomly selected subjects. Stereoacuity was transformed to log scale. 95% limits of agreement were calculated for test-retest reliability. The Bland-Altman plot was used to demonstrate the agreement between the tests and the examiners. RESULTS: The mean ± SD crossed distance stereoacuities using VDST in normal, intermittent exotropia and amblyopic children were 93.1 ± 43.8, 161.9 ± 89.8 and 236.3 ± 122.4 arcseconds, respectively. For uncrossed stereoacuity, these were 104.7 ± 54.0, 187.6 ± 89.6 and 265.5 ± 144.0 arcseconds, respectively. Crossed stereoacuity was significantly better than uncrossed stereoacuity. 95% limits of test-retest agreement for crossed and uncrossed stereoacuities using the VDST were 0.27 and 0.30, respectively. An exact test-retest match using VDST was 84% in normals and 77% in abnormals for crossed and 83% in normal and 74% in abnormal for uncrossed stereoacuities. CONCLUSION: VDST is a reliable, valid and easy-to-administer distance crossed and uncrossed stereoacuity measuring device. Further studies are required to establish the clinical importance of assessing these two forms stereoacuities in relation to various binocular vision disorders.

Comparison of biometric and refractive changes in intermittent exotropia with and without overminus lens therapy.

BACKGROUND: Overminus lens is an effective non-surgical treatment of intermittent exotropia (IXT). Whether this treatment causes development of myopia is recently debated. This study evaluated ocular biometric changes in IXT children treated with and without overminus lens. METHODS: Children with IXT were randomly assigned to control and overminus groups. Cycloplegic refraction, axial length and other parameters (keratometry, anterior chamber depth and lens thickness) were evaluated for up to 30 months and compared between the groups. Axial length to corneal curvature (AL/CR) ratio was examined as an indicator of myopia progression. Changes prior to and after overminus were also assessed in a subgroup. RESULTS: Mean age of the total 84 subjects (58% women) was 7.2 years (range 4-15 years). Baseline refractive and biometric parameters of 39 control and 45 overminus subjects were not significantly different. Mean±SD change in refraction was -0.34±0.45D in controls and -0.41±0.66D in overminus group (p=0.527). AL increased by 0.29±0.20 millimetre (mm) in controls and 0.28±0.23 mm in overminus group (p=0.766). In the subgroup, the changes before and after overminus therapy was not significantly different (p>0.05). AL/CR ratio was maintained from baseline to follow-up visit (p=0.298) in both groups. CONCLUSION: No significant differences in biometry or refraction were found between the two groups and before and after the therapy. We conclude that the overminus therapy in children, not accounting for other myopia risk factors, does not affect normal refractive growths.

Accommodative Lag Persistence in Treated Anisometropic, Strabismic, and Mixed Amblyopia.

Background: Amblyopic eyes typically exhibit greater lag of accommodation. Whether this improves after amblyopia treatment is inconclusive. The aim of this study is to report post-treatment accommodative response in amblyopia and to investigate if the lag is associated with visual acuity, treatment duration, and amblyopia type. Methods: Monocular and binocular accommodative responses were measured using Nott's method of dynamic retinoscopy in amblyopia of anisometropic, strabismic, and combined anisometropic-strabismic types and age-matched controls with normal vision. The results were compared using the nonparametric Wilcoxon signed ranks test. Linear regression analysis was used to examine association of the lag to refractive error, duration of therapy, and visual acuity. Results: Mean ± SD age of 46 amblyopic and 20 control subjects were 6.9 ± 1.8 and 6.9 ± 2.2 years, respectively. At the time of the study, 30 amblyopic subjects were receiving patching therapy and ceased in the remainder. In amblyopic eyes, mean ± SD monocular and binocular lags were 1.2 ± 0.6D and 1.0 ± 0.5D (p < 0.001), respectively, compared to 0.6 ± 0.3D and 0.5 ± 0.2D (p < 0.005), respectively, in nonamblyopic eyes and 0.4 ± 0.2D and 0.3 ± 0.2D (p=0.093), respectively, in the controls. By types, the monocular lag was significantly higher than the binocular lag (p=0.001) in mixed amblyopia (p=0.004); they were similar in anisometropic (p=0.283) and strabismic (p=0.743) amblyopia. Monocular lag was significantly correlated to BCVA (r = 0.46; p=0.001) and refraction (r = 0.42; p=0.001) but not to patching duration (r = 0.1; p=0.280). Conclusion: Inadequate accommodative response, a higher lag, persists in amblyopic eyes even after the treatment. Impaired accommodative response is partly determined by posttherapy visual acuity. Further studies investigating the effect of accommodative lag on visual recovery and whether optical correction of the deficiency may improve visual outcome of the treatment are recommended.

A case of non-traumatic Purpureocillium lilacinum (Paecilomyces lilacinus) endophthalmitis in a child.

PURPOSE: The aim of this report is to cover a novel presentation and subsequent management of Purpureocillium (Paecilomyces) oculomycosis in a child, and to review the available literature on Purpureocillium endophthalmitis. OBSERVATIONS: This report is of a four year old boy from Australia. There have been 13 previous reports of Purpureocillium endophthalmitis, comprising 30 adult cases. CONCLUSIONS: AND IMPORTANCE. Purpureocillium is an emerging ocular infection, associated with use of this fungus as a biological control agent. This case highlights the importance of early consideration of intraocular fluid sampling in a case of vitritis non-responsive to steroid treatment. statementThe first reported case of atraumatic Purpureocillium lilacinum endophthalmitis, occurring in a child. All published Purpureocillium endophthalmitis cases are reviewed.

Idiopathic intracranial hypertension in a child with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is known to be associated with hydrocephalus, but not with idiopathic intracranial hypertension (IIH). Case presentation: We describe such a case and propose the pathogenesis. We also discuss the challenges of diagnosis, treatment, and monitoring outcomes in this population that is already at high risk of vision loss from retinal dystrophy. CONCLUSION: IIH can result from a combination of risk factors in conjunction with the underlying dysfunctional cilia in BBS patients. Monitoring disease progression is difficult, and as such IIH may be underdiagnosed or missed. Management must be adjusted to account for BBS patients' impaired metabolic and renal physiology. It is important that clinicians be aware of these challenges in this vulnerable population, and regular monitoring should be done to avoid preventable vision loss.

Optimised minus lens overcorrection for paediatric intermittent exotropia: A randomised clinical trial.

BACKGROUND: Aim of this study was to evaluate the efficacy of a novel algorithm to customise overminus lens therapy in intermittent exotropia (IXT) based on clinical factors associated with control of the deviation. METHODS: Clinical parameters in IXT vary among individuals. Based on individual's physiological factors, an algorithm was developed. Children aged between 4 and 15 years with IXT were randomised into OML and observation groups. Participants in the observation group were corrected for any significant refractive error. IXT control score, angle of deviation, refraction, axial length and stereopsis were examined at baseline and follow up ranging between 6 and 15 months and compared. Compliance and tolerance to OML was determined by a symptom survey. RESULTS: The OML power ranged between -1.00D and - 6.25D. Of the total 141 participants (mean age 6.8 ± 2.5 year), 77 were in the OML and 66 were in observation group. IXT control score improved (mean difference - 2.5 ± 1.1; p < 0.001) and angle of deviation reduced (6.9 ± 7.2pd; p < 0.001) significantly in the OML group only. Compliance rate to OML wear was 80%; 90% never or rarely experienced asthenopia symptoms. Slightly greater myopic shift (-0.36 ± 0.53D vs. -0.18 ± 0.55D) and change in axial length (0.17 vs. 0.14 mm) were observed in the OML group, but these differences were not statistically significant. CONCLUSIONS: A customised OML, calculated using this novel algorithm was effective in improving distance control, angle of deviation and stereopsis. Glasses wear was highly tolerable.

Community based vision screening in preschool children; performance of the Spot Vision Screener and optotype testing.

BACKGROUND: Children's vision screening children commonly uses optotype-based visual acuity or instrument-based methods measuring amblyogenic risk factors (ARFs). OBJECTIVE: To compare the performance of the Spot Vision Screener (SVS) (PediaVision, Welch Allyn, NY) and a nurse-administered visual acuity screen (NVAS) in identifying ARFs and decreased visual acuity. METHODS: A prospective, cross-sectional population-based study of preschool children in South-East Queensland, Australia. Eligible participants had both forms of screening by trained community nurses. All children with an abnormal result by either method as well as a cohort of randomly selected children who passed both assessments were assessed at a tertiary paediatric ophthalmology clinic. RESULTS: Over a 10 month period, 2237 children (mean age; 64.4 ± 4.0 months) were screened from 38 schools. 6.4% of children failed SVS and 8.3% failed NVAS (with 3.8% overlap, failing both). The positive predictive value (PPV) in identifying either ARFs and/or reduced VA for the SVS and NVAS was 70.4% (95% Confidence Interval (CI): 61.6%-78.2%) and 60.5% (95% CI: 52.6%-67.9%) respectively. Highest PPV to detect either ARFs and/or reduced VA was achieved by a 'hybrid' method by combining failed NVAS and failed SVS: 91.0% (95% CI: 82.4 to 96.3) but this would risk children with sight impairment being missed in the community. CONCLUSION: To our knowledge, this is the first population-based study providing detailed comparative measures of diagnostic accuracy for NVAS and SVS in preschool children. One in ten preschool children failed one or both screens. A number of children who required ophthalmic intervention were missed if only one screening method was utilized.

Rapid Assessment of Avoidable Blindness and Willingness to Pay for Cataract Surgery in Tribal Region of Surat District of Gujarat State, India.

AIM: To estimate prevalence and causes of avoidable blindness among people ≥50 years and to assess willingness to pay (WTP) for cataract surgery in tribal region of south Gujarat, India. METHODS: A cross-sectional population based survey was conducted with 44 randomly selected clusters each having 50 people aged ≥50 years selected by probability proportional to size of sampling. Adults identified with cataract causing visual loss (<6/18) in any eye were interviewed to assess their WTP for surgery. RESULTS: Total of 2137 examined out of 2200 people enumerated (response rate 97.1%). The prevalence of blindness (Presenting Visual Acuity (PVA)<3/60 in better eye) was 2.23% (95% CI: 2.95%-1.51%). Cataract was main cause of blindness (67.3%) followed by corneal scarring (8.2%). Major barrier to cataract surgery cited by bilaterally blind people was lack of escort to the surgical facility (34.3%). Cataract surgical coverage (CSC) was 84.9% (eyes) and 92% (persons). Of the 492 people interviewed to assess WTP for their surgery, only 36.4% people were willing to pay. CONCLUSION: The tribal population has a high poverty profile in India. Within this group, cataract remains the main treatable cause of blindness despite a high CSC. Assessment of barriers suggested that a well-coordinated outreach programme with free transport facilities to the surgical facility is required along with strategies to improve accessibility and prioritising cataract blind in the community. One-third of people were willing to pay for their surgeries implying that cross subsidization or tier system could be feasible for eye care programme sustainability.

Autoinflammatory retinopathy in chronic infantile neurological cutaneous and articular (CINCA) syndrome.

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a rare autosomal dominant autoinflammatory disease. We report the cases of monozygotic twins with CINCA syndrome whose predominant ocular manifestation was inflammatory rod-cone retinal dystrophy. Atypically, there were significant differences between twins in phenotype severity, suggestive of epigenetic differences and/or involvement of environmental factors.

A novel rhodopsin point mutation, proline-170-histidine, associated with sectoral retinitis pigmentosa.

Identification and classification of all retinitis pigmentosa (RP) causing mutations contribute to a better understanding of disease variants. In this report we describe a New Zealand family, of European heritage, affected by a sectoral type RP phenotype in association with a novel rhodopsin mutation (proline-170-histidine) in a highly conserved site.

Glaucoma in southwest Nigeria: clinical presentation, family history and perceptions.

Knowledge of the presentation pattern of glaucoma helps in providing more understanding of the disease, leading to better control. The aim of this study was to determine the presentation pattern among newly diagnosed glaucoma patients in Lagos, Nigeria. This was a multicenter cross-sectional survey of newly diagnosed glaucoma patients, recruited over a four-week period. Socio-demographic characteristics, presenting history, awareness and perception on glaucoma, and basic examination findings were obtained. A total of 208 patients, including 90 (43.2 %) females with a mean age of 53.9 years were recruited. One hundred and forty-three (68.7 %) were self-referred patients with a mean duration of symptoms of 2.6 years. Fifty-five (26.4 %) patients gave a history of glaucoma in at least one family member. Ninety-five patients (45.7 %) were aware that glaucoma can cause visual loss, but 69 (72.6 %) out of these believed the visual loss is reversible. Seventy (33.7 %) patients had been previously diagnosed with glaucoma elsewhere. From the 208 patients, 35.5 % had visual impairment (presenting visual acuity [VA] of <6/18 in the better eye), while 15.5 % were blind (presenting VA in better eye <3/60). Lack of glaucoma awareness, positive family history and illiteracy were associated with late presentation of glaucoma. Late presentation is still a major concern among glaucoma patients in Southwest Nigeria, and there is a need to intensify present efforts aimed at increasing public awareness, emphasising the irreversible nature of the disease, as well as encouraging at-risk groups such as first-degree relatives to go for screening.

Surgical output and clinic burden of glaucoma in lagos, Nigeria.

PURPOSE: To estimate the outpatient clinic burden and surgical workload related to glaucoma in Lagos, Nigeria. METHODS: A multicentre study involving the 2 tertiary eye institutions, 7 secondary eye centers with eye care facilities, and the largest private eye hospital in Lagos state, Nigeria. Data on outpatient department (OPD) visits were collected over a 4-week period, using a specially designed tally sheet. Theater records were examined in each hospital over a 1-year period (2009) for the number and types of glaucoma surgeries performed. RESULTS: A total of 6240 patients visited the OPD over the 4-week period, out of which 1577 (25.3%) were glaucoma patients. OPD visit per ophthalmologist were 274, 323, and 61, whereas glaucoma visits per ophthalmologist were 75, 70, and 23 in the tertiary, secondary, and private centers, respectively. Glaucoma surgeries constituted 8.6% of total surgeries (n=4050). Trabeculectomy with intraoperative 5-fluorouracil was the most common procedure (81.0%). Number of glaucoma surgeries per ophthalmologist per month in the tertiary, secondary, and private centers were 0.5, 0.9, and 1.4, respectively. Overall number of glaucoma surgery per ophthalmologist per month was 1. CONCLUSIONS: Glaucoma visits constitute a significant proportion of eye clinic visits in Lagos state, Nigeria, and therefore, necessary manpower, infrastructure, and equipments should be mobilized for its optimal management. Also, there is a relatively low output of glaucoma surgeries that needs to be further investigated and appropriate measures taken to manage it.

Specialist Nurse Screening for Retinopathy of Prematurity-A Pilot Study.

PURPOSE: To compare the accuracy of retinopathy of prematurity (ROP) screening between nurse specialists and an expert pediatric ophthalmologist. DESIGN: A comparative case series of ROP screening in a level 2 neonatal intensive care unit setting where there is a higher threshold for accepting very premature or unwell neonates. METHODS: Trained specialist ROP nurses acquired wide-field digital images, graded ROP, and proposed a follow-up plan. This was compared with the findings by an ROP expert ophthalmologist. Outcomes include sensitivity, specificity, positive predictive value, and negative predictive value of ROP grading by trained ROP nurses. RESULTS: Mean gestational age was 28.6 weeks, and mean birth weight was 1184 g of the 64 consecutive neonates included. A total 316 eye screens was performed. Image acquisition, grading, and a management plan by the ROP nurse were possible in all screens. In right eyes, the presence of any ROP (stage >0) was 15%. Sensitivity, specificity, positive predictive value, and negative predictive value of ROP grading were 91.7% (95% CI, 73%-99%), 80.6% (95% CI, 72.9%-86.9%), 45.8% (95% CI, 31.4%-60.80%), and 98.2% (95% CI, 93.6%-99.8%), respectively. Agreement on the management plan occurred in 84.8% of cases. In virtually all circumstances of disagreement, ROP nurses exaggerated the ROP grading present and/or recommended a repeat screen when discharge from service was more appropriate. CONCLUSIONS: Our preliminary findings demonstrated good agreement between ROP nurses and the ROP expert ophthalmologist. Further research in expanding the role of utilizing nonphysician health workers in ROP screening is suggested.

Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management.

PURPOSE: To describe the clinical features of children with anophthalmos, microphthalmos, and typical coloboma (AMC). DESIGN: Descriptive, observational, cross-sectional study of the United Kingdom. PARTICIPANTS: A total of 135 children with AMC newly diagnosed over an 18-month period beginning in October 2006. METHODS: Cases were identified using active surveillance through an established ophthalmic surveillance system. Eligible cases were followed up 6 months after first notification. MAIN OUTCOME MEASURES: Phenotypic characteristics, both ocular and systemic, clinical investigations, causes, and interventions. RESULTS: A total of 210 eyes (of 135 children) were affected by AMC, of which 153 had isolated coloboma or coloboma with microphthalmos. The most common colobomatous anomaly was a chorioretinal defect present in 109 eyes (71.2%). Some 44% of children were bilaterally visually impaired. Systemic abnormalities were present in 59.7% of children, with craniofacial anomalies being the most common. Children with bilateral disease had a 2.7 times higher odds (95% confidence interval, 1.3-5.5, P = 0.006) of having systemic involvement than unilaterally affected children. Neurologic imaging was the most frequent investigation (58.5%) performed. Less than one third (30.3%) of the children with microphthalmos had ocular axial lengths measured. Eight children had confirmed genetic mutations. Approximately half (49.2%) of the children required ocular intervention. CONCLUSIONS: Colobomatous defects were the most common phenotype within this spectrum of anomalies in the United Kingdom. The high frequency of posterior segment colobomatous involvement means that a dilated fundal examination should be made in all cases. The significant visual and systemic morbidity in affected children underlines the importance of a multidisciplinary approach to management.