Variability of retinopathy consequent upon novel mutations in LAMA1.

PURPOSE: Bi-allelic mutations in LAMA1 (laminin 1) (OMIM # 150320) cause Poretti-Boltshauser Syndrome (PTBHS), a rare non-progressive cerebellar dysplasia disorder with ophthalmic manifestations including oculomotor apraxia, high myopia, and retinal dystrophy. Only 38 variants, nearly all loss of function have been reported. Here, we describe novel LAMA1 variants and detailed retinal manifestations in two unrelated families. METHODS: Whole-genome sequencing was conducted on three siblings of a consanguineous family with myopia and retinal dystrophy and on a child from an unrelated non-consanguineous couple. Clinical evaluation included full ophthalmic examination, detailed colour, autofluorescence retinal imaging, retinal optical coherence tomography (OCT), fluorescein angiography under anesthesia, and pattern and full-field electroretinography. RESULTS: Genetic analysis revealed a novel homozygous LAMA1 frameshift variant, c.1492del p.(Arg498Glyfs *25), in the affected siblings in family 1 and a novel frameshift c.3065del p.(Gly1022Valfs *2) and a deletion spanning exons 17-23 in an unrelated individual in family 2. Two of the three siblings and the unrelated child had oculomotor apraxia in childhood; none of the siblings had symptoms of other neurological dysfunction as adults. All four had myopia. The affected siblings had a qualitatively similar retinopathy of wide-ranging severity. The unrelated patient had a severe abnormality of retinal vascular development, which resulted in vitreous haemorrhage and neovascular glaucoma in the left eye and a rhegmatogenous retinal detachment in the right eye. CONCLUSIONS: This report describes the detailed retinal structural and functional consequences of LAMA1 deficiency in four patients from two families, and these exhibit significant variability with evidence of both retinal dystrophy and abnormal and incomplete retinal vascularisation.

Accuracy of scleral transillumination techniques to identify infant ciliary body for sclerostomy and intravitreal injections.

IMPORTANCE: There is variation in the literature for sclerotomy and intravitreal injection placement in young children, ranging from 0.5 to 3.0 mm from the limbus. We assess the accuracy of scleral transillumination to identify the ciliary body in infants for safe sclerotomy and intravitreal injections in young children. BACKGROUND: The study compares the perilimbal "dark band" seen on scleral transillumination (STI) with the ultrasound biomicroscopy (UBM), and compares these measurements with the current guidelines for sclerotomy in infants. DESIGN: Prospective case series in a tertiary paediatric hospital. PARTICIPANTS: Children aged ≤36 months undergoing general anaesthesia for eye procedures. METHODS: Scleral transillumination was performed to measure the perilimbal dark band. UBM of the ciliary body region was then performed, and correlated with transillumination findings. MAIN OUTCOME MEASURES: The midpoints of STI and UBM were compared to current cadaver-based guidelines to assess the safe point for sclerotomy. RESULTS: Twenty children were recruited, 36 STI and 35 UBM measurements were obtained. The posterior edge of the dark band had good correlation with the posterior border of the ciliary body. Transillumination and UBM correlated well for midpoint measurements. The midpoint of the dark band on transillumination was confirmed to be in the ciliary body by UBM in all cases. CONCLUSIONS AND RELEVANCE: The STI technique is a useful and fast technique to demonstrate the ciliary body. The midpoint of the dark band on STI correlates well with the UBM, and has a potential use for confirming safe-entry into the posterior segment if using current guidelines. The current cadaver-based paediatric guidelines safely avoid retinal injury.

RETINAL DETACHMENT AND RETROBULBAR CYSTS IN A LARGE COHORT OF OPTIC NERVE COLOBOMA.

PURPOSE: To examine the relationship between retinal detachment and retrobulbar cysts in patients with optic nerve coloboma (ONC) and Morning Glory syndrome (MGS). METHODS: Patients diagnosed with either ONC or MGS were identified through a search of the Sick Kids database. Seventy-one patients either agreed to come in for a B-scan or had an incidental orbital B-scan or magnetic resonance imaging or both. Eyes with orbital B-scan ultrasound and/or magnetic resonance imaging images were assessed independently by two ophthalmologists and a radiologist for the presence of retrobulbar cysts. Retinal detachment was identified clinically with either indirect ophthalmoscopy or from fundus photographs. RESULTS: Forty-five of 71 (63%) and 26/71 (37%) patients had ONC and MGS, respectively. Retinal detachment occurred significantly more often in eyes with MGS than with ONC (9/17 [53%] vs. 5/45 [11%], P = 0.03, respectively). Retrobulbar cysts were not detected more often in MGS than in ONC (11/45 [24%] vs. 7/26 [27%]; P = 1.0). Eyes with retrobulbar cysts were significantly more likely to be associated with retinal detachment than those without (7/18 [39%] vs. 7/53 [13%]; P = 0.04). CONCLUSION: Retinal detachment occurs more frequently in MGS than in ONC in a cohort of patients referred to a specialist children's retinal service. Eyes with retrobulbar cysts are more likely to be associated with retinal detachment.

Non-contact ultra-widefield retinal imaging of infants with suspected abusive head trauma.

PurposeThe purpose of the study was to audit the use of non-contact ultra-widefield retinal imaging in infants with suspected abusive head trauma (AHT) using the Optos P200MA Scanning Laser Ophthalmoscope.Patients and methodsA retrospective, observational case series. Ten eyes of five consecutive infants (aged 1-15 months) with suspected (or in 1 case, known) AHT referred for an ophthalmological opinion were included. Each infant underwent non-contact ultra-widefield retinal imaging using the Optos P200MA scanning laser ophthalmoscope. Optos fundus fluorescein angiography (FFA) was performed in one infant with oral sedation. The other four infants did not require sedation. The main outcome measure was the acquisition of a single, definitive ultra-widefield retinal image in each eye. Safety was audited by determining adverse changes in heart rate and oxygen saturations that required cessation of imaging.ResultsThe Optos P200MA ultra-widefield scanning laser ophthalmoscope acquired good quality retinal images in all infants. Documentation of acute, widespread retinal haemorrhages contributed to a diagnosis of AHT in three infants. Chronic pre-macular haemorrhage and macular schisis were documented by FFA in a fourth infant. The absence of retinal haemorrhages was documented in a fifth infant contributing to the exclusion of a diagnosis of AHT. There were no adverse safety signals in any infant in this series.ConclusionThe Optos P200MA ultra-widefield scanning laser ophthalmoscope appears safe to use in infants with suspected AHT, providing high-quality retinal images in a single frame without ocular contact. Optos P200MA may be used as alternative to RetCam to document retinal haemorrhages in stable infants with suspected AHT.

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study.

PURPOSE: To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. DESIGN: International, multicenter, interventional, retrospective case series. PARTICIPANTS: Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. METHODS: Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. MAIN OUTCOME MEASURES: Ocular and systemic adverse events. RESULTS: A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. CONCLUSIONS: This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Risk factors for retinal detachment following cataract surgery: the impact of posterior capsular rupture.

AIM: To investigate risk factors for retinal detachment (RD) after cataract surgery, particularly posterior capsular rupture (PCR) with or without vitreous loss. METHODS: Single centre electronic medical record database study of 18 065 consecutive first eye cataract operations performed between 2005 and 2014. Survival analysis was performed with Kaplan-Meier curves and a Cox proportional hazard regression analysis to calculate HRs with respect to RD. RESULTS: The RD rate at 3 months and 7 years was 0.067% and 0.30%, respectively, with a median time to RD of 15 months (mean: 18 months, range: 0-84 months). Men had a higher RD risk (HR 2.00; 95% CI 1.03 to 3.88; p=0.03) in the univariate model. Patients <60 years and those >80 years had an HR of 5.12 (95% CI 2.60 to 10.07; p<0.001) and 0.16 (95% CI 0.38 to 0.69; p=0.01), respectively, compared with patients 60-80 years of age. Eyes longer than 25 mm had an HR of 3.98 (95% CI 1.93 to 8.20; p<0.001) compared with eyes 23-25 mm. PCR occurred in 400 (2.2%) eyes. The HR for RD was 12.83 (95% CI 5.62 to 29.30; p<0.001) for PCR with vitreous loss. There were no RD events in eyes with PCR without vitreous loss. CONCLUSIONS: The risk for RD after cataract surgery is higher in younger patients and eyes with longer axial length or PCR with vitreous loss during surgery.

EXTENT AND LOCATION OF INTRARETINAL AND SUBRETINAL FLUID AS PROGNOSTIC FACTORS FOR THE OUTCOME OF PATIENTS WITH OPTIC DISK PIT MACULOPATHY.

PURPOSE: To determine if baseline fundoscopic and optical coherence tomography (OCT) features influence the clinical course of optic disk pit maculopathy. METHODS: A multicenter retrospective case note review was undertaken, using standardized OCT and clinical data collection. Visual success was defined as at least a two-line visual acuity improvement, anatomical success as full resolution of OCT foveal fluid with restoration of the normal foveal contour, and partial anatomical success as incomplete resolution of the OCT foveal fluid. Outcomes were compared with a synthesis of the literature, using similar eligibility criteria. RESULTS: Of 36 patients (36 eyes), 2 spontaneously improved and 34 underwent surgery. Visual success was achieved in 64% of surgical cases, anatomical success in 36%, and partial anatomical success in 47%. Cases with multilayer intraretinal and subretinal fluid were less likely to have visual success (P = 0.003). Cases where the fluid did not extend to the macular arcade vessels also had better visual and anatomical outcomes (P = 0.004 and 0.005, respectively). CONCLUSION: Fundoscopic and OCT features can help predict surgical outcome in optic disk pit maculopathy.

Incidence and treatment of retinopathy of prematurity in England between 1990 and 2011: database study.

AIMS: To study the incidence and treatment of retinopathy of prematurity (ROP) in England, 1990-2011. METHODS: English national Hospital Episode Statistics were analysed, for babies born in hospital and for inpatient admissions, to obtain annual rates of diagnosis of, and treatment for, babies with ROP. National data on low birthweight (LBW) babies, born <1500 g and therefore eligible for ROP screening, were used as denominators in calculating rates of ROP per 1000 babies at risk. RESULTS: The recorded incidence of ROP increased tenfold, from 12.8 per 1000 LBW babies in 1990 to 125.5 per 1000 LBW babies in 2011. Tretment rates for ROP by cryotherapy or laser rose from 1.7 to 14.8 per 1000 LBW babies between 1990 and 2011. In 1990, 13.3% of babies with ROP were treated with cryotherapy, which fell to 0.1% in 2011. Rates for laser treatment rose from 1.8% of babies with ROP in 1999 to 11.7% in 2011. CONCLUSIONS: Increased neonatal survival, improved awareness of ROP and dissemination of guidance on screening and treatment of ROP will all have contributed to the substantial rise in recorded incidence of ROP between 1990 and 2011. Retinal ablation is now almost always performed using laser treatment rather than cryotherapy.

Multifocal Necrotizing Chorioretinitis Following Phacoemulsification Surgery.

INTRODUCTION: Toxoplasma chorioretinitis is a leading cause of infectious posterior uveitis worldwide. METHODS: We report an atypical presentation of Toxoplasma chorioretinitis presenting after uneventful cataract surgery in an 81-year-old male, with known hypernephroma and rheumatoid arthritis, treated with prednisolone and methotrexate. RESULTS: He was treated for acute retinal necrosis and cytomegalovirus retinitis before Toxoplasma chorioretinitis was confirmed by vitreous biopsy 11 months after presentation. He developed a secondary rhegmatogenous retinal detachment, treated successfully with pars plana vitrectomy, silicone oil and endolaser. Visual acuity at discharge was 6/12 following silicone oil removal. DISCUSSION: Necrotising chorioretinitis in immunosuppressed or elderly patients may present with an atypical phenotype. Clinical diagnosis in this context remains challenging. We discuss the clinical reasoning behind investigation and management of this patient group in whom viral and Toxoplasma retinitis may be clinically indistinguishable. The significance of vitreous PCR results in clinical decision making in the context of infectious posterior uveitis is discussed.

Transient retinal artery occlusion during phacoemulsification cataract surgery.

PURPOSE: Transient retinal artery occlusion (TRAO) is a potentially underdiagnosed cause of immediate 'pad off' visual loss following phacoemulsification cataract surgery under sub-Tenon's anaesthesia. METHODS: We describe a series of three patients presenting with enigmatic 'pad off' visual loss following phacoemulsification surgery, each diagnosed with TRAO. We describe the variable clinical presentation, illustrate the value of optical coherence tomography (OCT) imaging in establishing the diagnosis, and present the final visual outcomes. RESULTS: Clinical findings alone may be subtle and inadequate in localising the pathology in patients with TRAO. Cross-comparison of superior and inferior macula OCT profiles in branch-pattern arterial occlusion-and between healthy and affected eyes in central-pattern arteriolar occlusion-is critical in clinching the diagnosis. The typical evolution of OCT appearance is acute-phase inner retinal thickening/oedema and hyperreflectivity followed by progressive, late-phase inner retinal atrophy. Visual acuity may recover but central scotomas, and defects in colour perception may persist. CONCLUSION: The diagnosis of TRAO is challenging; delayed presentation may resolve fundal and retinal angiographic abnormalities. OCT may be the only imaging modality that can provide objective evidence of TRAO. Meticulous comparison/segmentation of OCT images is therefore mandatory in patients presenting with acute post-operative visual loss to exclude TRAO.

Outpatient Ultra wide-field intravenous fundus fluorescein angiography in infants using the Optos P200MA scanning laser ophthalmoscope.

PURPOSE: To determine the feasibility of Ultra wide-field intravenous fundus fluorescein angiography (UWF-IV-FFA) in infants. METHODS: A retrospective review of infants who underwent UWF-IV-FFA with the Optos P200MA was performed. The ability to capture different phases of the angiogram, the total image acquisition time and the presence of image artefacts were analysed. RESULTS: Twelve infants with a variety of proliferative retinopathies underwent UWF-IV-FFA over a 7-month period. The mean age was 3.4 months (range 2-6 months) and the mean image acquisition time was 4 min (range 3-5). Pseudocolour fundus images and the venous, recirculation and late phases of UWF-IV-FFA were captured successfully in all infants (100%). Choroidal and arterial phases were captured in one (8.3%) and 10 (83.3%) infants, respectively. Image artefacts due to eyelashes and corneal desiccation occurred in nine (75%) and six (50%) infants, respectively. No adverse medical problems were noted. CONCLUSIONS: We have shown that UWF-IV-FFA can be successfully and safely performed in infants using the Optos P200MA system. It is a feasible new alternative to RetCam for obtaining an IV-FFA in the outpatients setting.

Bimanual anterior segment revision surgery for anterior capsule contraction syndrome associated with anterior flexion of intraocular lens haptics.

PURPOSE: To report the incidence of anterior capsule contraction syndrome (ACCS) and to present a novel minimally invasive bimanual technique for anterior segment revision surgery associated with ACCS with anterior flexion of the intraocular lens haptics. METHODS: A consecutive cohort of 268 eyes of 161 patients undergoing phacoemulsification and implantation of the same type of hydrophilic acrylic aspheric intraocular lens cohort were analysed and a novel technique of minimally invasive bimanual technique for anterior segment revision surgery is described. RESULTS: We identified four eyes (1.5%) of three patients with advanced ACCS. Successful restoration of a clear visual axis with minimal induction of astigmatism and rapid visual rehabilitation was achieved in all four cases. CONCLUSION: This technique is a safe and minimally invasive alternative to laser or vitrector-cut capsulotomy to restore a clear visual axis. In cases of advanced ACCS, it offers the option for haptic reposition or amputation.