Publications by authors named "John R Grigg"

70 Publications

A case of neurofibromatosis type 1 and unilateral glaucoma with ectropion uveae.

Ophthalmic Genet 2022 Jun 20:1-4. Epub 2022 Jun 20.

Save Sight Institute, Discipline of Clinical Ophthalmology and Eye Health, Faculty of Medicine and Health, Sydney, NSW, Australia.

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http://dx.doi.org/10.1080/13816810.2022.2089362DOI Listing
June 2022

Electrophysiological Assessment in Birdshot Chorioretinopathy: Flicker Electroretinograms Recorded With a Handheld Device.

Transl Vis Sci Technol 2022 05;11(5):23

Section of Ophthalmology, King's College London, London, UK.

Purpose: The flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals.

Methods: Non-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers. At one center (group 1), the stimuli (85 Td·s, 850 Td background) delivered retinal illuminance equivalent to international standards; at the other center (group 2), a different protocol was used (32 Td·s, no background). Patients also underwent international standard flicker ERG recordings with conventional electrodes following mydriasis. Portable ERGs from patients were also compared with those from healthy individuals.

Results: Thirty-two patients with BCR (mean age ± SD, 56.4 ± 11.3 years) underwent recordings. Portable and standard ERG parameters correlated strongly (r > 0.75, P < 0.01) in both groups. Limits of agreement for peak times were tighter in group 1 (n = 21; -4.3 to +2.0 ms [right eyes], -3.9 to 1.5 ms [left eyes]) than in group 2 (n = 11; -3.4 to +6.9 ms [right eyes], -4.8 to +9.0 ms [left eyes]). Compared with healthy controls (n = 66 and n = 90 for groups 1 and 2, respectively), patients with BCR showed smaller mean amplitudes and longer peak times.

Conclusions: Portable ERGs correlated strongly with conventional recordings, suggesting potential in rapid assessment of cone system function in office settings.

Translational Relevance: Flicker ERGs, known to be useful in BCR, can be obtained rapidly with a portable device with skin electrodes and natural pupils.
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http://dx.doi.org/10.1167/tvst.11.5.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145202PMC
May 2022

Whole Genome Sequencing, Focused Assays and Functional Studies Increasing Understanding in Cryptic Inherited Retinal Dystrophies.

Int J Mol Sci 2022 Mar 31;23(7). Epub 2022 Mar 31.

Eye Genetics Research Unit, Sydney Children's Hospitals Network, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, NSW 2000, Australia.

The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy. In this study, we investigated whole genome sequencing (WGS), focused assays and functional studies to assist with unsolved IRD cases and facilitate integration of these approaches to a broad molecular diagnostic clinical service. The WGS approach identified variants not covered or underinvestigated by targeted capture panel-based clinical testing strategies in six families. This included structural variants, with notable benefit of the WGS approach in repetitive regions demonstrated by a family with a hybrid gene and hemizygous missense variant involving the opsin genes, and . There was also benefit in investigation of the repetitive GC-rich ORF15 region of . Further molecular investigations were facilitated by focused assays in these regions. Deep intronic variants were identified in and , with functional RNA based studies of the variant revealing activation of a cryptic splice acceptor site. While targeted capture panel-based methods are successful in achieving an efficient molecular diagnosis in a proportion of cases, this study highlights the additional benefit and clinical value that may be derived from WGS, focused assays and functional genomics in the highly heterogeneous IRDs.
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http://dx.doi.org/10.3390/ijms23073905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999823PMC
March 2022

Human iPSC-Derived Retinal Organoids and Retinal Pigment Epithelium for Novel Intronic Variant Assessment for Therapy Suitability.

J Pers Med 2022 Mar 21;12(3). Epub 2022 Mar 21.

Eye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Westmead, Sydney 2145, Australia.

The gene encodes Retinitis Pigmentosa GTPase Regulator, a known interactor with ciliary proteins, which is involved in maintaining healthy photoreceptor cells. Variants in are the main contributor to X-linked rod-cone dystrophy (RCD), and gene therapy approaches are in clinical trials. Hence, elucidation of the pathogenicity of novel variants is important for a patient therapy opportunity. Here, we describe a novel intronic variant, c.1415 - 9A>G, in a patient with RCD, which was classified as a variant of uncertain significance according to current clinical diagnostic criteria. The variant lay several base pairs intronic to the canonical splice acceptor site, raising suspicion of an RNA splicing abnormality and consequent protein dysfunction. To investigate disease causation in an appropriate disease model, induced pluripotent stem cells were generated from patient fibroblasts and differentiated to retinal pigment epithelium (iPSC-RPE) and retinal organoids (iPSC-RO). Abnormal RNA splicing of was demonstrated in patient fibroblasts, iPSC-RPE and iPSC-ROs, leading to a predicted frameshift and premature stop codon. Decreased RPGR expression was demonstrated in these cell types, with a striking loss of RPGR localization at the ciliary transitional zone, critically in the photoreceptor cilium of the patient iPSC-ROs. Mislocalisation of rhodopsin staining was present in the patient's iPSC-RO rod photoreceptor cells, along with an abnormality of L/M opsin staining affecting cone photoreceptor cells and increased photoreceptor apoptosis. Additionally, patient iPSC-ROs displayed an increase in F-actin expression that was consistent with an abnormal actin regulation phenotype. Collectively, these studies indicate that the splicing abnormality caused by the c.1415 - 9A>G variant has an impact on RPGR function. This work has enabled the reclassification of this variant to pathogenic, allowing the consideration of patients with this variant having access to gene therapy clinical trials. In addition, we have identified biomarkers of disease suitable for the interrogation of other variants of uncertain significance.
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http://dx.doi.org/10.3390/jpm12030502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951517PMC
March 2022

Electronegative electroretinogram in the modern multimodal imaging era.

Clin Exp Ophthalmol 2022 05 8;50(4):429-440. Epub 2022 Mar 8.

Visual electrophysiology Unit, Save Sight Institute, Speciality of Clinical Ophthalmology and Eye Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Background: The electronegative electroretinogram (ERG) reflecting inner retinal dysfunction can assist as a diagnostic tool to determine the anatomical location in eye disease. The aim of this study is to determine the frequency and aetiology of electronegative ERG in a tertiary ophthalmology centre and to develop a clinical algorithm to assist patient management.

Methods: Retrospective review of ERGs performed at the Save Sight Institute from January 2011 to December 2020. ERGs were performed according to ISCEV standard. The b:a ratio was analysed in dark adapted (DA) 3.0 or 12.0 recordings. Patients with ratio of ≤1.0 were included.

Results: A total of 4421 patients had ERGs performed during study period, of which 139 patients (3.1%) had electronegative ERG. The electronegative ERG patients' median age at referral time was 37 (0.7-90.6) years. The causative aetiologies were photoreceptor dystrophy (48, 34.5%), Congenital Stationary Night Blindness (CSNB) (33, 23.7%), retinal ischemia (18, 12.9%), retinoschisis (15, 10.8%), paraneoplastic autoimmune retinopathy (PAIR) and nonPAIR (14, 10.1%), batten disease (4, 2.9%), and inflammatory retinopathy (4, 2.9%). There were three patients with an unclassified diagnosis. Thirty-two patients (23%) had good vision and a normal fundus appearance. Eleven patients (7.9%) had good vision and normal results in all multimodal imaging.

Conclusions: The frequency of electronegative ERG in our referral centre was 3.1% with photoreceptor dystrophy as the main aetiology. A significant number of the cases had good vision with normal fundus or normal multimodal imaging. This further highlights the value of an ERG in this modern multimodal imaging era.
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http://dx.doi.org/10.1111/ceo.14065DOI Listing
May 2022

Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials.

Surv Ophthalmol 2022 Jul-Aug;67(4):1270-1286. Epub 2022 Jan 31.

Moorfields Eye Hospital, London, United Kingdom; Institute of Ophthalmology, University College London, United Kingdom; Section of Ophthalmology, King's College London, St Thomas' Hospital Campus, London, United Kingdom; Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.

The study of individual differences in perception at absolute threshold has a rich history, with much of the seminal work being driven by the need to identify those with superior abilities in times of war. Although the popularity of such testing waned in the latter half of the 20th century, interest in measures of visual function at the absolute limit of vision is increasing, partly in response to emerging treatments for retinal diseases, such as gene therapy and cellular therapies, that demand "new" functional measures to assess treatment outcomes. Conventional clinical, or clinical research, testing approaches generally assess rod sensitivity at or near absolute threshold; however, cone sensitivity is typically assayed in the presence of adapting backgrounds. This asymmetry may artifactually favor the detection of rod abnormalities in patients with outer retinal disease. The past decade has seen the commercialization of devices capable of assessing absolute threshold and dark adaptation, including specialized perimeters and instruments capable of assessing "full-field sensitivity threshold" that seek to integrate responses over time and space in those with unstable fixation and/or limited visual fields. Finally, there has also been a recent recapitulation of tests that seek to assess the subject's ability to interpret the visual scene at or near absolute threshold. In addition to assessing vision, such tests simultaneously place cognitive and motor demands on patients in line with the activities of daily living they seek to replicate. We describe the physical and physiological basis of absolute threshold and dark adaptation. Furthermore, we discuss experimental psychophysical and electrophysiological approaches to studying vision at absolute threshold and provide a brief overview of clinical tests of vision at absolute threshold.
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http://dx.doi.org/10.1016/j.survophthal.2022.01.008DOI Listing
January 2022

Approach to childhood glaucoma: A review.

Clin Exp Ophthalmol 2022 03 25;50(2):232-246. Epub 2022 Jan 25.

Speciality of Ophthalmology, Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Childhood glaucoma represents a heterogenous group of rare ocular conditions that may result in significant sight threatening complications related to elevated intraocular pressure (IOP). It can be classified as either primary or secondary and the latter may have systemic associations. This review will be based on the work of the childhood glaucoma research network (CGRN) and will focus on the diagnosis and management of the most common types of childhood glaucoma. These include primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG) as well as secondary causes of glaucoma associated with non-acquired ocular anomalies (Axenfeld-Rieger anomaly; Peters anomaly and Aniridia), glaucoma associated with systemic disease (Sturge Weber syndrome and Neurofibromatosis), those due to acquired conditions (Uveitic glaucoma, trauma and tumours) and importantly glaucoma following cataract surgery.
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http://dx.doi.org/10.1111/ceo.14039DOI Listing
March 2022

Safety and biocompatibility of a bionic eye: Imaging, intraocular pressure, and histology data.

Data Brief 2021 Dec 26;39:107634. Epub 2021 Nov 26.

School of Biomedical Engineering, Faculty of Engineering, University of Sydney, Sydney, Australia.

The data presented here are related and supplementary data to the research article "Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep" [1]. In Eggenberger et al., nine sheep of the Suffolk (N=2) and Dorper (N=7) breeds were implanted in the left eye with an electrically inactive, suprachoroidal retinal stimulator (Bionic Eye) for durations of up to 100 days. The surgical safety, implant stability and device biocompatibility were assessed. Intraocular pressure measurements, indirect and infrared ophthalmoscopy and optical coherence tomography were performed at fixed time points to evaluate the clinical effects of the surgery and device implantation. Post-mortem eye tissue collection and histology was performed to measure the effects of the intervention at the cellular level. The data, including a comprehensive collection of fundus, infrared, optical coherence tomography and histology images can be used as a reference for comparison with other research, for example, active retinal stimulators. Furthermore, these data can be used to evaluate the suitability of the sheep model, in particular Dorper sheep, for future research.
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http://dx.doi.org/10.1016/j.dib.2021.107634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711049PMC
December 2021

Evaluation for Retinal Therapy for Variation Assessed in hiPSC Retinal Pigment Epithelial Cells.

Stem Cells Int 2021 13;2021:4536382. Epub 2021 Dec 13.

Eye Genetics Research Unit, Sydney Children's Hospitals Network-Westmead, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.

Human induced pluripotent stem cells (hiPSCs) generated from patients and the derivative retinal cells enable the investigation of pathological and novel variants in relevant cell populations. Biallelic pathogenic variants in cause early-onset severe retinal dystrophy (EOSRD) or Leber congenital amaurosis (LCA). Increasingly, regulatory-approved retinal gene replacement therapy is available for patients with these clinical features, but only if they have biallelic pathological variants and sufficient viable retinal cells. In our cohort of patients, we identified siblings with early-onset severe retinal degeneration where genomic studies revealed compound heterozygous variants in , one a known pathogenic missense variant and the other a novel synonymous variant of uncertain significance. The synonymous variant was suspected to affect RNA splicing. Since RPE65 is very poorly expressed in all tissues except the retinal pigment epithelium (RPE), we generated hiPSC-derived RPE cells from the parental carrier of the synonymous variant. Sequencing of RNA obtained from hiPSC-RPE cells demonstrated heterozygous skipping of exon 2 and the introduction of a premature stop codon in the mRNA. Minigene studies confirmed the splicing aberration. Results from this study led to reclassification of the synonymous variant to a pathogenic variant, providing the affected patients with access to gene replacement therapy.
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http://dx.doi.org/10.1155/2021/4536382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687838PMC
December 2021

Cataract Surgery in Short Eyes, Including Nanophthalmos: Visual Outcomes, Complications and Refractive Results.

Clin Ophthalmol 2021 27;15:4543-4551. Epub 2021 Nov 27.

Save Sight Institute, University of Sydney, Sydney, NSW, Australia.

Background: To report the visual outcomes, complications and refractive results of phacoemulsification surgery and intraocular lens implantation in a large series of adult patients with short and nanophthalmic eyes.

Methods: The records of all patients with axial length <21.0 mm undergoing phacoemulsification with intraocular lens implantation at an adult teaching hospital were retrospectively reviewed. The main outcome measures were corrected distance visual acuity and refraction at 90 days after surgery and intra- and postoperative complications occurring during the follow-up period.

Results: A total of 71 eyes of 51 patients (median age 71 years, interquartile range 62-75.5) were included. Surgery resulted in an improvement in corrected distance visual acuity in 53 eyes (74.6%) (95% confidence interval, logMAR 0.11-0.29) and was logMAR 0.30 or better in 47 eyes (66.2%). Worsening of corrected distance visual acuity occurred in 9 eyes (12.7%). Median postoperative refractive error was -0.75 dioptres. SRK/T and Kane formula were more accurate in predicting postoperative refraction than Barrett Universal II and Hoffer Q when based on mean absolute error ( < 0.005). Complications occurred in 18 eyes (25.4%). The most frequent complications were iris prolapse, Descemet's membrane and/or endothelial trauma, transient severe corneal edema and cystoid macular edema. There was no statistically significant difference in complication rates between senior surgeons and senior trainees ( = 0.66).

Conclusion: Cataract surgery in short and nanophthalmic eyes is challenging with a higher complication rate than routine cataract surgery, but frequently results in good visual outcomes. Postoperative refractive outcomes are more difficult to predict in this cohort.
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http://dx.doi.org/10.2147/OPTH.S344465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636843PMC
November 2021

Barriers and facilitators to diabetic retinopathy screening within Australian primary care.

BMC Fam Pract 2021 11 30;22(1):239. Epub 2021 Nov 30.

The Australian e-Health Research Centre, CSIRO, 147 Underwood Avenue, Floreat, WA, 6014, Australia.

Background: Despite recent incentives through Medicare (Australia's universal health insurance scheme) to increase retinal screening rates in primary care, comprehensive diabetic retinopathy (DR) screening has not been reached in Australia. The current study aimed to identify key factors affecting the delivery of diabetic retinopathy (DR) screening in Australian general practices.

Methods: A descriptive qualitative study involving in-depth interviews was carried out from November 2019 to March 2020. Using purposive snowballing sampling, 15 general practitioners (GPs) were recruited from urban and rural general practices in New South Wales and Western Australia. A semi-structured interview guide was used to collect data from participants. All interviews were conducted over the phone by one facilitator, and each interview lasted up to 45 min. The Socio-Ecological Model was used to inform the content of the interview topic guides and subsequent data analysis. Recorded data were transcribed verbatim, and thematic analysis was conducted to identify and classify recurrent themes.

Results: Of 15 GPs interviewed, 13 were male doctors, and the mean age was 54.7 ± 15.5 years. Seven participants were practising in urban areas, while eight were practising in regional or remote areas. All participants had access to a direct ophthalmoscope, but none owned retinal cameras. None of the participants reported performing DR screening. Only three participants were aware of the Medicare Benefits Schedule (MBS) items 12,325 and 12,326 that allow GPs to bill for retinal screening. Seven themes, a combination of facilitators and barriers, emerged from interviews with the GPs. Despite the strong belief in their role in managing chronic diseases, barriers such as costs of retinal cameras, time constraints, lack of skills to make DR diagnosis, and unawareness of Medicare incentives for non-mydriatic retinal photography made it difficult to conduct DR screening in general practice. However, several enabling strategies to deliver DR screening within primary care include increasing GPs' access to continuing professional development, subsidising the cost of retinal cameras, and the need for a champion ace to take the responsibility of retinal photography.

Conclusion: This study identified essential areas at the system level that require addressing to promote the broader implementation of DR screening, in particular, a nationwide awareness campaign to maximise the use of MBS items, improve GPs' competency, and subsidise costs of the retinal cameras for small and rural general practices.
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http://dx.doi.org/10.1186/s12875-021-01586-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630186PMC
November 2021

Efficient capture of high-quality real-world data on treatments for glaucoma: the Fight Glaucoma Blindness! Registry.

BMJ Open Ophthalmol 2021 5;6(1):e000903. Epub 2021 Nov 5.

Clinical Ophthalmology & Eye Health, The University of Sydney, Sydney, New South Wales, Australia.

Objective: To describe the development and implementation of a web-based high-quality data collection tool to track the outcomes of glaucoma treatments in routine practice.

Methods And Analysis: This is a prospective observational registry study. An international steering committee undertook an iterative structured process to define a minimum, patient-centred data set designed to track outcomes of glaucoma treatment. The outcomes were coded into a web-based programme allowing easy access for rapid data entry. Clinicians receive personal reports enabling instant audit of their outcomes. Analyses of aggregated anonymised data on real-world outcomes are analysed and periodically reported with the goal of improving patient care.

Results: The minimum data set developed by the international steering committee includes the following: a baseline visit captures 13 mandatory fields in order to accurately phenotype each patient's subtype of glaucoma and to allow comparison between services, and a follow-up visit includes only four mandatory fields to allow completion within 30 s.Currently, there are 157 surgeons in 158 ophthalmology practices across Australia and New Zealand who are registered. These surgeons are tracking 5570 eyes of 3001 patients and have recorded 67 074 visits. The median number of eyes per surgeon is 22 eyes with a range of 1-575. The most common glaucoma procedure, excluding cataract surgery, is iStent inject, with 2316 cases.

Conclusion: This software tool effectively facilitates data collection on safety and efficacy outcomes of treatments for different subgroups of glaucoma within a real-world setting. It provides a template to evaluate new treatments as they are introduced into practice.
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http://dx.doi.org/10.1136/bmjophth-2021-000903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573655PMC
November 2021

Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep.

Biomaterials 2021 12 22;279:121191. Epub 2021 Oct 22.

School of Biomedical Engineering, Faculty of Engineering, University of Sydney, Sydney, Australia; Graduate School of Biomedical Engineering, University of New South Wales (UNSW), Sydney, Australia. Electronic address:

Severe visual impairment can result from retinal degenerative diseases such as retinitis pigmentosa, which lead to photoreceptor cell death. These pathologies result in extensive neural and glial remodelling, with survival of excitable retinal neurons that can be electrically stimulated to elicit visual percepts and restore a form of useful vision. The Phoenix Bionic Eye is a fully implantable visual prosthesis, designed to stimulate the retina from the suprachoroidal space. In the current study, nine passive devices were implanted in an ovine model from two days to three months. The impact of the intervention and implant stability were assessed using indirect ophthalmoscopy, infrared imaging, and optical coherence tomography to establish the safety profile of the surgery and the device. The biocompatibility of the device was evaluated using histopathological analysis of the tissue surrounding the electrode array, with a focus on the health of the retinal cells required to convey signals to the brain. Appropriate stability of the electrode array was demonstrated, and histological analysis shows that the fibrotic and inflammatory response to the array was mild. Promising evidence of the safety and potential of the Phoenix Bionic Eye to restore a sense of vision to the severely visually impaired was obtained.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121191DOI Listing
December 2021

retinopathy: biomarkers assessing vision loss.

Ophthalmic Genet 2021 12 22;42(6):706-716. Epub 2021 Jul 22.

Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Purpose: Mer tyrosine kinase-retinitis pigmentosa (RP) causes a primary defect in the retinal pigment epithelium, which subsequently affects rod and cone photoreceptors. The study aims to identify the most appropriate -RP biomarkers to measure disease progression for deciding the optimum therapeutic trial intervention time.

Materials And Methods: Patients' data from baseline (BL) and last follow-up (LFU) were reviewed. Best corrected visual acuity (BCVA), spectral domain-optical coherence tomography (SD-OCT), ultra-widefield fundus autofluorescence (UWF-FAF) patterns, kinetic perimetry (KP), and electroretinography (ERG) parameters were analyzed.

Results: Five patients were included with the mean age of 17.7 ± 14.4 years old (6.7-42.3) at BL and mean BCVA follow-up of 8.4 ± 5.1 years. Mean BCVA at BL and LFU were 0.84 ± 0.86 LogMAR and 1.14 ± 0.86 LogMAR, respectively. The BCVA decline rate was 0.05 ± 0.03 LogMAR units/year. Ellipzoid zones (EZ) were measurable in eight eyes with mean BL length of 1293.75 ± 421.07 µm and reduction of 140.95 ± 69.28 µm/year and mean BL CMT of 174.2 ± 37.52 µm with the rate of 11.2 ± 12.77 µm declining/year. Full-field ERG (ffERG) and pattern ERG (pERG) were barely recordable. UWF-FAF showed central macular hyper-autofluorescence (hyperAF). KP (III4e and V4e) was normal in two eyes, restricted nasally in four eyes, superior wedge defect in two eyes and undetectable in two eyes. The four restricted nasally KPs became worse, while the others stayed almost unchanged.

Conclusions: This cohort showed early visual loss, moderately rapid EZ reduction and macular hyperAF. EZ, CMT, and BCVA were consistently reduced. Relative rapid decline in these biomarkers reflecting visual function suggests an early and narrow timespan for intervention.
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http://dx.doi.org/10.1080/13816810.2021.1955278DOI Listing
December 2021

The electroretinogram in the genomics era: outer retinal disorders.

Eye (Lond) 2021 09 7;35(9):2406-2418. Epub 2021 Jul 7.

Visual Electrophysiology Unit, Save Sight Institute, Speciality of Clinical Ophthalmology and Eye Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

The inherited retinal diseases (IRDs) have traditionally been described phenotypically with the description evolving to incorporate more sophisticated structural and functional assessments. In the last 25 years there has been considerable advances in the understanding of underlying genetic aetiologies. The role of the ophthalmologist is now to work in a multi-disciplinary team to identify the disease-causing genotype, which might be amenable to gene-directed intervention. Visual electrophysiology is an important tool to assist the ophthalmologist in guiding the clinical geneticist to reach a final molecular diagnosis. This review outlines the physiological basis for the ISCEV standard electrophysiology tests, the role of electrophysiology in localising the functional deficit, correlation with structural findings to guide diagnosis and finally management of IRDs in the era of genomics with emphasis on the outer retina.
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http://dx.doi.org/10.1038/s41433-021-01659-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377088PMC
September 2021

Genome sequencing in congenital cataracts improves diagnostic yield.

Hum Mutat 2021 09 15;42(9):1173-1183. Epub 2021 Jun 15.

Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.

Congenital cataracts are one of the major causes of childhood-onset blindness around the world. Genetic diagnosis provides benefits through avoidance of unnecessary tests, surveillance of extraocular features, and genetic family information. In this study, we demonstrate the value of genome sequencing in improving diagnostic yield in congenital cataract patients and families. We applied genome sequencing to investigate 20 probands with congenital cataracts. We examined the added value of genome sequencing across a total cohort of 52 probands, including 14 unable to be diagnosed using previous microarray and exome or panel-based approaches. Although exome or genome sequencing would have detected the variants in 35/52 (67%) of the cases, specific advantages of genome sequencing led to additional diagnoses in 10% (5/52) of the overall cohort, and we achieved an overall diagnostic rate of 77% (40/52). Specific benefits of genome sequencing were due to detection of small copy number variants (2), indels in repetitive regions (2) or single-nucleotide variants (SNVs) in GC-rich regions (1), not detectable on the previous microarray, exome sequencing, or panel-based approaches. In other cases, SNVs were identified in cataract disease genes, including those newly identified since our previous study. This study highlights the additional yield of genome sequencing in congenital cataracts.
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http://dx.doi.org/10.1002/humu.24240DOI Listing
September 2021

Heterozygous COL9A3 variants cause severe peripheral vitreoretinal degeneration and retinal detachment.

Eur J Hum Genet 2021 05 25;29(5):881-886. Epub 2021 Feb 25.

Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.

The COL9A3 gene encodes one of the three alpha chains of Type IX collagen, with heterozygous variants reported to cause multiple epiphyseal dysplasia, and suggested as contributory in some cases of sensorineural hearing loss. Patients with homozygous variants have midface hypoplasia, myopia, sensorineural hearing loss, epiphyseal changes and carry a diagnosis of Stickler syndrome. Variants in COL9A3 have not previously been reported to cause vitreoretinal degeneration and/or retinal detachments. This report describes two families with autosomal dominant inheritance and predominant features of peripheral vitreoretinal lattice degeneration and retinal detachment. Genomic sequencing revealed a heterozygous splice variant in COL9A3 [NG_016353.1(NM_001853.4):c.1107 + 1G>C, NC_000020.10(NM_001853.4):c.1107 + 1G>C, LRG1253t1] in Family 1, and a heterozygous missense variant [NG_016353.1(NM_001853.4):c.388G>A p.(Gly130Ser)] in Family 2, each segregating with disease. cDNA studies of the splice variant demonstrated an in-frame deletion in the COL2 domain, and the missense variant occurred in the COL3 domain, both indicating the critical role of Type IX collagen in the vitreous base of the eye.
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http://dx.doi.org/10.1038/s41431-021-00820-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110976PMC
May 2021

Assessing Residual Cone Function in Retinitis Pigmentosa Patients.

Transl Vis Sci Technol 2020 12 17;9(13):29. Epub 2020 Dec 17.

Save Sight Institute, The Discipline of Clinical Ophthalmology and Eye Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Purpose: The purpose of this study was to investigate cone function deterioration in patients with retinitis pigmentosa (RP) using full field electroretinogram (ffERG), pattern electroretinogram (pERG), and optical coherence tomography (OCT) and their correlation with visual acuity (VA).

Methods: Clinical records (2008-2018) of patients with RP undergoing repeat electrophysiology were reviewed. Results of ffERG (30 Hz flicker and fused flicker amplitude [FFAmp]), pERG [p50 and n95], and macular OCT (ellipsoid zone [EZ] and outer segment thickness) were collected.

Results: One hundred twenty-six eyes from 63 patients (33 women, mean age 35 years) were included. The mean decline in VA was 0.11 ± 0.14 logarithm of minimum angle of resolution (logMAR). The FFAmp decreased by 3.01 ± 5.9 µV with global cone function deteriorating by 18.7% annually. The percentage change in FFAmp (RE [ = 0.553], LE [ = 0.531]), and 30 Hz flicker amplitude (RE [ = 0.615], LE [ = 0.529]) strongly correlated with VA ( < 0.00001). The pERG p50 (15 and 30 degrees) change analyzed in 34 patients showed reduction by 23% and 23.4%, respectively. The percentage change in p50 30 degrees ( = 0.397) correlated with VA and EZ layer ( < 0.05). The EZ layer change was calculated in 45 patients and the shortening and thinning rate was 4.3% and 4.4% annually, respectively. The EZ length percentage change correlated with VA (RE [ = 0.34] and LE [ = 0.466; < 0.05).

Conclusions: We quantified the decline in cone function in patients with RP utilizing ffERG and FFAmp measures of residual cone function. These parameters correlated with VA and OCT when measurable. These objective measures may assist in monitoring disease progression.

Translational Relevance: Residual cone function provides an objective estimate of residual visual function, which aids in counselling patients regarding prognosis.
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http://dx.doi.org/10.1167/tvst.9.13.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746956PMC
December 2020

Natural history and clinical biomarkers of progression in X-linked retinitis pigmentosa: a systematic review.

Acta Ophthalmol 2021 Aug 30;99(5):499-510. Epub 2020 Nov 30.

Save Sight Institute, Discipline of Ophthalmology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

X-linked retinitis pigmentosa (XLRP) accounts for a significant proportion of certifiable blindness in working-age adults. The objectives of this study were to: (1) synthesize the best available evidence regarding the natural history of disease progression and (2) identify the best current clinical biomarkers for monitoring disease progression, which will be important in planned gene therapy trials for this condition. Patient population: XLRP affected males. Main outcomes: A systematic review of the literature was undertaken with data sought on overall annual progression for clinical biomarkers using optical coherence tomography (OCT), fundus autofluorescence (FAF), visual acuity, electroretinography and visual fields. To assess which outcome was best for monitoring progression, data on reliability, interocular correlation and structure-function correlation were extracted. A total of 17 studies met the inclusion criteria. Studies estimated progression at between 4% to 19% per year with longitudinal data. Where an overall model was produced with cross-sectional data, the trend was usually best fit by a logarithmic function with an annual exponential decline rate between 4.7% and 8.0%. The evidence suggested the ellipsoid zone (EZ) width on OCT and outer ring area (ORA) on FAF as the most useful biomarkers having excellent interocular symmetry, reproducibility and functional correlation. Using different clinical biomarkers, XLRP progresses at a rate of 4 to 19% per year. Ellipsoid zone (EZ) width and ORA are the most robust biomarkers with the potential to be used in trials where one eye serves as a control for the other.
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http://dx.doi.org/10.1111/aos.14662DOI Listing
August 2021

Surgical Treatment for SWS Glaucoma: Experience From a Tertiary Referral Pediatric Hospital.

J Glaucoma 2020 12;29(12):1132-1137

Discipline of Ophthalmology, Save Sight Institute.

Precis: Glaucoma associated with Sturge-Weber syndrome (SWS) often requires surgical intervention. Our study shows that trabeculectomy is efficacious in treating this condition.

Purpose: The purpose of this study was to describe the surgical outcomes of glaucoma associated with SWS in children presenting to the tertiary Paediatric Ophthalmology Department at The Children's Hospital at Westmead.

Materials And Methods: A retrospective study of patients with SWS referred to the Department of Ophthalmology at The Children's Hospital at Westmead between 2003 and 2016 with at least 2 years of follow-up were identified, and information was collected from the clinical notes of all subjects.

Results: A total of 27 patients with SWS were evaluated for glaucoma in which 8 were excluded due to inadequate follow-up. In total, 19 patients with SWS were included in this study in which glaucoma was diagnosed in 15 patients and 19 eyes, of which 13 eyes required glaucoma surgery. A total of 21 surgical procedures were performed with a median follow-up of 85 months. A primary trabeculotomy was performed in 5 eyes of which 4 required re-do trabeculotomy, and 3 of these eyes underwent a Baerveldt tube (BVT) shunt as a third procedure. One eye with a primary trabeculotomy underwent a BVT as a secondary procedure. A BVT was inserted in a total of 6 eyes in which it was a primary procedure in 2 eyes. Of the 6 eyes undergoing a BVT insertion, 5 achieved success (2 complete and 3 qualified), and 1 failed. One case underwent intraluminal stent removal. Six eyes underwent a primary trabeculectomy and needed no further surgical intervention. In the trabeculectomy group, 4 eyes achieved complete success and 2 eyes achieved qualified success.

Conclusions: Glaucoma affects a significant proportion of patients with SWS and is associated with the presence of an ipsilateral port-wine stain in most cases. In our study, trabeculectomy was the most efficacious procedure for controlling intraocular pressure and reducing the burden of ongoing treatment in SWS-associated glaucoma.
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http://dx.doi.org/10.1097/IJG.0000000000001645DOI Listing
December 2020

Response to: "Comment on: 'Comparison of perimetric glaucoma staging systems in Asians with primary glaucoma'".

Eye (Lond) 2021 08 21;35(8):2327-2328. Epub 2020 Aug 21.

Save Sight Institute, The University of Sydney School of Medicine, Sydney, NSW, Australia.

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http://dx.doi.org/10.1038/s41433-020-01149-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302556PMC
August 2021

Does functional assessment predict everyday visual functioning? Visual function testing and quality of life in mild/moderate age-related macular degeneration.

Int Ophthalmol 2020 Dec 14;40(12):3241-3249. Epub 2020 Jul 14.

Save Sight Institute, The University of Sydney, Sydney, Australia.

Purpose: To prospectively assess correlations between self-reported vision-related quality of life (VR-QoL) and clinical functional assessments in mild/moderate age-related macular degeneration (AMD).

Methods: Cross-sectional analysis of 64 participants with bilateral mild/moderate AMD. Microperimetry (MP), flicker perimetry (FP), multifocal electroretinogram (mfERG) findings, best-corrected visual acuity (BCVA) and the National Eye Institute Visual-Function Questionnaire-25 (NEI VFQ-25) were assessed for correlation between clinical testing results and NEI VFQ-25 findings.

Results: MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p < 0.05 and R < 0.3 for all). FP findings and mfERG response density were not correlated with any subscale, apart from mfERG ring 1 response density and general health (p < 0.05, R = 0.41). mfERG latency was weakly correlated with general vision in the better eye in rings 2 and 4 (p < 0.05, R < 0.2).

Conclusion: Functional assessment in mild/moderate AMD is at best, weakly correlated with patient-reported VR-QoL. Despite the growing awareness of the importance of VR-QoL outcomes in improving patient outcomes and satisfaction, surrogate markers of these outcomes remain elusive, and testing of VR-QoL in regular clinical settings remains difficult.
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http://dx.doi.org/10.1007/s10792-020-01508-zDOI Listing
December 2020

Comparison of perimetric Glaucoma Staging Systems in Asians with primary glaucoma.

Eye (Lond) 2021 Mar 9;35(3):973-978. Epub 2020 Jun 9.

Save Sight Institute, The University of Sydney School of Medicine, Camperdown, NSW, Australia.

Background: To compare functional staging classifications in Vietnamese patients with primary open angle glaucoma (POAG) and chronic primary angle closure glaucoma (PACG).

Methods: A retrospective cross-section study was conducted at a national setting. Two hundred seven eyes of 207 patients were recruited. Patients were tested with standard automated perimetry. Field loss was generally classified in four stages (normal, early, moderate, and severe), using four classification strategies: (1) Hodapp-Parrish-Anderson (HPA), (2) enhanced Glaucoma Staging System (eGSS), (3) modified Glaucoma Staging System (mGSS) and (4) the Advanced Glaucoma Intervention Study (AGIS). AGIS as a standard method was used to judge the staging performance of the other three classifications in terms of agreement (Cohen Kappa-K) and association (Chi-Square Test-Cramer's V).

Results: The agreement between AGIS and mGSS (K = 0.687; p < 0.001) and HPA (K = 0.686; p < 0.001) was substantial while that between AGIS and eGSS was slight (K = 0.103; p < 0.001). The association between AGIS and mGSS (V = 0.748; p < 0.001) and HPA (V = 0.748; p < 0.001) was greater than eGSS (V = 0.594; p < 0.001).

Conclusions: MGSS and HPA showed stronger agreement and closer association with AGIS than eGSS. We recommend mGSS should be used in managing a glaucoma clinic because of its simplicity and convenience over HPA and AGIS.
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http://dx.doi.org/10.1038/s41433-020-1012-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027002PMC
March 2021

Revealing hidden genetic diagnoses in the ocular anterior segment disorders.

Genet Med 2020 10 5;22(10):1623-1632. Epub 2020 Jun 5.

Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.

Purpose: Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion.

Methods: We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases.

Results: We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6.

Conclusions: We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously "hidden" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes.
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http://dx.doi.org/10.1038/s41436-020-0854-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521990PMC
October 2020

Outcome measures in juvenile X-linked retinoschisis: A systematic review.

Eye (Lond) 2020 10 20;34(10):1760-1769. Epub 2020 Apr 20.

Discipline of Clinical Ophthalmology and Eye Health, Faculty of Medicine and Health, Save Sight Institute, 8 Macquarie Street, Sydney, NSW, 2001, Australia.

X-linked retinoschisis (XLRS) is a leading cause of hereditary juvenile macular degeneration in males resulting in significant vision impairment. Outcome measures to monitor disease progression or therapeutic interventions have evolved with technology. A systematic review was undertaken to evaluate outcome measures for XLRS. Inclusion criteria were all publications examining outcome measures for natural history studies or following an interventional approach for patients with XLRS. Studies which did not present follow-up data were excluded. We searched medical databases including CENTRAL, Ovid Medline, pre-Medline and ahead of Print up to February 2019. Two authors independently assessed the risk of bias. Twelve studies meet the inclusion criteria with four prospective and eight retrospective case series. Five series were natural history observational studies and seven were interventional series using either topical or systemic carbonic anhydrase inhibitors. Visual acuity (VA) declined very slowly in the natural history studies equivalent to 0.22-0.5 letters per year. Five of the six interventional studies showed an improvement in VA and four a reduction in spectral domain optical coherence tomography (SD-OCT) parameters for central macular thickness (CMT). The full-field electroretinogram identified the 30-Hz latency as a further parameter to monitor function. VA was the measure most likely to show a statistically significant outcome. How functionally meaningful this is, requires further evaluation. CMT SD-OCT outcomes are variable depending on cystic changes. More refined measures are required to better correlate structure with function.
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http://dx.doi.org/10.1038/s41433-020-0848-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608480PMC
October 2020

Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings.

Doc Ophthalmol 2020 12 2;141(3):205-215. Epub 2020 Apr 2.

The Discipline of Clinical Ophthalmology and Eye Health, Save Sight Institute, Sydney Eye Hospital, Faculty of Medicine and Health, The University of Sydney, 8 Macquarie Street, Sydney, NSW, 2001, Australia.

Purpose: To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH).

Methods: Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers-macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus.

Results: Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 ± 0.3 LogMAR. MI extent was significantly associated with better vision (β = - 0.175 per 1000 µm; R = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (β = 782 per µV; R = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (β = - 499 per µV; R = 0.219; P = 0.030). Mean CMT was 271 ± 35 μm and was significantly associated with better vision (β = - 0.083 per 10 µm; R = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 ± 0.2 LogMAR) and without CME (0.40 ± 0.5; R = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns.

Conclusions: Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.
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http://dx.doi.org/10.1007/s10633-020-09765-0DOI Listing
December 2020

UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES.

Retin Cases Brief Rep 2021 Nov;15(6):718-723

Sydney Eye Hospital, Sydney, New South Wales, Australia.

Background/purpose: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma.

Methods: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified.

Results: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment.

Conclusion: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.
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http://dx.doi.org/10.1097/ICB.0000000000000876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542090PMC
November 2021

The changing face of the ciliary body in the paediatric population.

Clin Exp Ophthalmol 2019 05;47(4):435-436

The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/ceo.13556DOI Listing
May 2019

ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.

Genet Med 2019 09 10;21(9):2103-2115. Epub 2019 Apr 10.

Drs. Farley, Polo and Ho, Colonial Heights, VA, USA.

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache.

Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members.

Results: We found the heterozygous missense variant in the ɑ-kinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis.

Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.
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http://dx.doi.org/10.1038/s41436-019-0476-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752478PMC
September 2019

Changing biological disease modifying treatment for paediatric uveitis in the real world.

Clin Exp Ophthalmol 2019 08 27;47(6):741-748. Epub 2019 Mar 27.

Department of Ophthalmology, Sydney Eye Hospital, Sydney, Australia.

Importance: Paediatric uveitis is a severe sight-threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real-world data on their use from Sydney, Australia.

Background: Traditionally corticosteroids and non-biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes.

Design: Retrospective, chart review over an 8-year period at a tertiary referral eye hospital.

Participants: A total of 27 paediatric uveitis patients treated with biological agents.

Methods: Chart review of demographic data and treatment outcomes.

Main Outcome Measures: Treatment efficacy (corticosteroid-sparing effect, topical steroid cessation/reduction, reduction in systemic-steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months.

Results: Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid-sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction.

Conclusions And Relevance: Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.
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http://dx.doi.org/10.1111/ceo.13494DOI Listing
August 2019
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