The role of artificial intelligence in macular hole management: A scoping review.

NARRATIVE ABSTRACT: We focus on the utility of artificial intelligence (AI) in the management of macular hole (MH). We synthesize 25 studies, comprehensively reporting on each AI model's development strategy, validation, tasks, performance, strengths, and limitations. All models analyzed ophthalmic images, and 5 (20 %) also analyzed clinical features. Study objectives were categorized based on 3 stages of MH care: diagnosis, identification of MH characteristics, and postoperative predictions of hole closure and vision recovery. Twenty-two (88 %) AI models underwent supervised learning, and the models were most often deployed to determine a MH diagnosis. None of the articles applied AI to guiding treatment plans. AI model performance was compared to other algorithms and to human graders. Of the 10 studies comparing AI to human graders (i.e., retinal specialists, general ophthalmologists, and ophthalmology trainees), 5 (50 %) reported equivalent or higher performance. Overall, AI analysis of images and clinical characteristics in MH demonstrated high diagnostic and predictive accuracy. Convolutional neural networks comprised the majority of included AI models, including those which were high performing. Future research may consider validating algorithms to propose personalized treatment plans and explore clinical use of the aforementioned algorithms.

Optogenetics and Targeted Gene Therapy for Retinal Diseases: Unravelling the Fundamentals, Applications, and Future Perspectives.

With a common aim of restoring physiological function of defective cells, optogenetics and targeted gene therapies have shown great clinical potential and novelty in the branch of personalized medicine and inherited retinal diseases (IRDs). The basis of optogenetics aims to bypass defective photoreceptors by introducing opsins with light-sensing capabilities. In contrast, targeted gene therapies, such as methods based on CRISPR-Cas9 and RNA interference with noncoding RNAs (i.e., microRNA, small interfering RNA, short hairpin RNA), consists of inducing normal gene or protein expression into affected cells. Having partially leveraged the challenges limiting their prompt introduction into the clinical practice (i.e., engineering, cell or tissue delivery capabilities), it is crucial to deepen the fields of knowledge applied to optogenetics and targeted gene therapy. The aim of this in-depth and novel literature review is to explain the fundamentals and applications of optogenetics and targeted gene therapies, while providing decision-making arguments for ophthalmologists. First, we review the biomolecular principles and engineering steps involved in optogenetics and the targeted gene therapies mentioned above by bringing a focus on the specific vectors and molecules for cell signalization. The importance of vector choice and engineering methods are discussed. Second, we summarize the ongoing clinical trials and most recent discoveries for optogenetics and targeted gene therapies for IRDs. Finally, we then discuss the limits and current challenges of each novel therapy. We aim to provide for the first time scientific-based explanations for clinicians to justify the specificity of each therapy for one disease, which can help improve clinical decision-making tasks.

Exploring the impact of Choroideremia on women with phenotypic and/or genotypic evidence of disease: insights from a global survey.

INTRODUCTION: Choroideremia (CHM) is an X-linked inherited retinal disease mostly affecting males. However, women with phenotypic and/or genotypic evidence of CHM may develop degenerative visual disability with advancing age. Our objective was to determine the visual impacts of phenotypic and/or genotypic evidence of CHM in women and its associated psychosocial burden and influence on activities of daily living (ADLs). METHODS: We conducted an international cross-sectional survey from April to December 2022 using an e-questionnaire distributed through not-for-profit stakeholder organizations and social media plat-forms. RESULTS: With a total of 55 respondents (n = 55), most women with phenotypic and/or genotypic evidence of CHM (76%) reported a change in their visual acuity. When assessing its impact on ADLs, Pearson's correlation coefficient showed a negative correlation between driving (p = 0.046) and mobility capabil-ities (0.046) with the respondent's age. More than half of women reported being afraid, anxious, and stressed, with women below the age of 50 years old reporting a significantly higher level of distress and hopelessness (p = 0.003), anxiety (p = 0.00007), issues with relaxing (p = 0.025), and negative personal thoughts (p = 0.042). CONCLUSION: Overall, this survey outlines both physical and psychological burden of being a woman with phenotypic and/or genotypic evidence of CHM. Given the limited clinical research in females affected by CHM, this patient-centered survey is a crucial advocacy tool for these individuals.

Impact of inherited retinal diseases on Canadian patients and families: a mixed-methods study.

OBJECTIVE: To understand the physical, psychosocial, and practical challenges faced by Canadian patients with inherited retinal diseases (IRDs) and their families. DESIGN: Mixed methods. PARTICIPANTS: A total of 408 Canadians living with or caring for someone with an IRD (mean age = 51.4 ± 16.7 years) completed an online survey. Twenty cohort respondents participated in additional telephone interviews. METHODS: The online survey was comprised of questions concerning demographics, self-reported vision, genetic testing, information preferences, health care experiences, treatment goals, and disease impact on daily life. Recruitment occurred through Fighting Blindness Canada's community database. Survey dissemination also occurred via social media and not-for-profit stakeholder outreach. Subsequent to survey completion, a subset of respondents participated in semistructured telephone interviews to further elucidate illness experience. RESULTS: Respondents identified having 1 of more than 14 IRDs, with 72% specifying retinitis pigmentosa. Sixty-eight percent reported being legally blind, and more than 85% self-reported moderate to low vision or worse. IRDs impacted daily functioning, with 53% of respondents indicating that they affected employment or education. Psychological challenges were evident, with more than 70% worried about coping with daily life and more than 60% indicating fear and stress. Qualitative data described hopelessness around suitable work, loss of independence, and challenges with social interaction. Sixty-five percent reported a negative impact on family life. Many had not accessed social support services because of a lack of perceived need, awareness, or availability. CONCLUSION: Canadian patients with IRDs report moderate to severe visual impairment, and both patients and their families describe an impact on psychosocial well-being and functioning during daily activities. Vision rehabilitation with a psychosocial approach is necessary, alongside facilitating access to emerging treatments.

Resting state electroretinography: An innovative approach to intrinsic retinal function monitoring.

The electroretinogram (ERG) represents the biopotential evoked by the retina in response to a light stimulus. The flash evoked ERG (fERG) is the ERG modality most frequently used clinically to diagnose and monitor retinal disorders. We hereby present a new method to record spontaneous retinal activity, without the use of a flash stimulus, that we named the resting-state ERG (rsERG). The recordings were done in normal subjects under light- and dark-adaptation and with different background light conditions (i.e., variations of wavelength and intensity). Additionally, rsERG recordings were obtained in five patients with retinopathies. The signals were subsequently analyzed in the frequency domain, extracting both periodic (i.e., frequency peaks) and aperiodic (i.e., background trend) components of the signal. The later was further assessed through a multifractal analysis using Wavelet Leaders. Results show that, irrespective of the recording conditions used, the rsERG always includes the same 90 Hz component; a frequency component also present in the fERG response, suggesting a retinally-intrinsic origin. However, in addition, the fERGs also includes a low-frequency component which is absent in the rsERGs, a finding supporting a retinally-induced origin. Comparing rsERGs with fERGs in selected patients with various retinal disorders indicates that the two retinal signals are not always similarly affected (either as a result of underlying retinal pathology or otherwise), suggesting an added value in the assessment of retinal function. Thus, the rsERG could have a similar role in clinical visual electrophysiology as that of the resting-state EEG in neurology namely, to quantify changes in spontaneous activity that result from a given disease processes.

Repair of Rhegmatogenous Retinal Detachment in Choroideremia Secondary to Posterior Extramacular Retinal Hole.

Rhegmatogenous retinal detachment in choroideremia is a rare occurrence. The authors present a case of a 23-year-old man with choroideremia with a near-total rhegmatogenous retinal detachment. Fundus examination did not reveal any retinal breaks, but extensive preoperative optical coherence tomography detected a small posterior hole along the superior arcades. The retinal detachment was successfully managed with vitrectomy, perfluorooctane to confirm the absence of any peripheral breaks, endolaser, and 20% sulfur hexafluoride gas. Similar extramacular holes were found in the patient's other eye. Patients with choroideremia may develop posterior retinal breaks leading to retinal detachment.

PCDH12 variants are associated with basal ganglia anomalies and exudative vitreoretinopathy.

PCDH12 is a member of the non-clustered protocadherins that mediate cell-cell adhesion, playing crucial roles in many biological processes. Among these, PCDH12 promotes cell-cell interactions at inter-endothelial junctions, exerting essential functions in vascular homeostasis and angiogenesis. However, its exact role in eye vascular and brain development is not completely understood. To date, biallelic loss of function variants in PCDH12 have been associated with a neurodevelopmental disorder characterized by the typical neuroradiological findings of diencephalic-mesencephalic junction dysplasia and intracranial calcifications, whereas heterozygous variants have been recently linked to isolated brain calcifications in absence of cognitive impairment or other brain malformations. Recently, the phenotypic spectrum associated with PCDH12 deficiency has been expanded including cerebellar and eye abnormalities. Here, we report two female siblings harboring a novel frameshift homozygous variant (c.2169delT, p.(Val724TyrfsTer8)) in PCDH12. In addition to the typical diencephalic-mesencephalic junction dysplasia, brain MRI showed dysmorphic basal ganglia and thalamus that were reminiscent of a tubulin-like phenotype, mild cerebellar vermis hypoplasia and extensive prominence of perivascular spaces in both siblings. The oldest sister developed profound and progressive monocular visual loss and the eye exam revealed exudative vitreoretinopathy. Similar but milder eye changes were also noted in her younger sister. In summary, our report expands the clinical (brain and ocular) spectrum of PCDH12-related disorders and adds a further line of evidence underscoring the important role of PCDH12 in retinal vascular and brain development.

Non-communicable disease risk factors and management among internal migrant in China: systematic review and meta-analysis.

BACKGROUND: In 2019, there are more than 290 million people who have ever migrated from rural to urban areas in China. These rural-to-urban internal migrants account for more than one-fifth of China's population and is the largest internal migrant group globally. We present the first systematic review that examines whether internal migrants are more likely to exhibit non-communicable diseases (NCDs) risk factors and have worse NCD management outcomes than non-migrant counterparts in China. METHODS: A systematic review was conducted via medical, public health, and economic databases including Scopus, MEDLINE, JSTOR, WHO Library Database and World Bank e-Library from 2000 to 2020. Study quality was assessed using the National Institute of Health Quality Assessment tool. We conducted a narrative review and synthesised differences for all studies included, stratified by different types of outcomes. We also conducted random-effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO: CRD42019139407. RESULTS: For most NCD risk factors and care cascade management, comparisons between internal migrants and other populations were either statistically insignificant or inconclusive. While most studies found migrants have a higher prevalence of tobacco use than urban residents, these differences were not statistically significant in the meta-analysis. Although three out four studies suggested that migrants may have worse access to NCD treatment and both studies suggested migrants have lower blood pressure control rates than non-migrants, these findings were not statistically significant. CONCLUSION: Findings from this systematic review demonstrate that there is currently insufficient evidence on migrant and non-migrant differences in NCD risk factors and management in China. Further research is expected to investigate access to healthcare among internal and its effect on both their NCD outcomes and long-term healthcare costs in China.

Durability of VEGF Suppression With Intravitreal Aflibercept and Brolucizumab: Using Pharmacokinetic Modeling to Understand Clinical Outcomes.

Purpose: To investigate whether vascular endothelial growth factor (VEGF)-suppression durations contribute to our understanding of clinical trial outcomes by simulating vitreous molar concentrations (Cvm) of intravitreal aflibercept (IVT-AFL) and brolucizumab (IVT-BRO) using pharmacokinetic (PK) modeling. Methods: A PK model simulated Cvm after single-dose IVT-AFL, IVT-BRO, and ranibizumab (IVT-RAN), and extrapolated intraocular VEGF-suppression thresholds and durations. Vitreous PK after multidose regimens used in studies of IVT-AFL versus IVT-BRO were simulated and compared with best-corrected visual acuity (BCVA) data. Results: Cvm peaked higher (Cmax) and decreased more quickly to the VEGF-suppression threshold and minimum (Cmin) levels with IVT-BRO than with IVT-AFL, consistent with their molar doses calculated using molecular weights and vitreous half-lives (26 kDa and 115 kDa; 4.4-5.1 and 9.1-11 days, respectively). The mean VEGF suppression durations were 71 days for IVT-AFL 2 mg and 51 (48-59) days for IVT-BRO 6 mg. Based on dosing in OSPREY (matched dosing to week [w]32 for both agents; thereafter, IVT-AFL every eight weeks [q8w] and IVT-BRO q12w for the last two doses [w32→w44 and w44→w56]), IVT-BRO showed wider Cmax-Cmin fluctuations than IVT-AFL. The IVT-BRO Cmin fell below the VEGF-suppression threshold at timepoints near w56, when decreases in BCVA were also observed. The IVT-AFL vitreous Cmin remained above the suppression threshold through w56, where BCVA gains were maintained. Conclusions: The PK-modeled mean VEGF-suppression duration for IVT-BRO was substantially shorter than that published for IVT-AFL and may not be sufficient to effectively suppress VEGF throughout q12w dosing. Translational Relevance: The PK modeling suggests that more patients may be maintained on ≥q12w dosing with IVT-AFL than with IVT-BRO.

Imaging Biomarkers and Their Impact on Therapeutic Decision-Making in the Management of Neovascular Age-Related Macular Degeneration.

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Coats-like Exudative Vitreoretinopathy in Retinitis Pigmentosa: Ocular Manifestations and Treatment Outcomes.

PURPOSE: To provide a comprehensive review of the ocular manifestations, outcomes, and genetic findings in patients with Coats-like retinitis pigmentosa (RP). DESIGN: Multicenter, retrospective, nonconsecutive case series. PARTICIPANTS: Patients with a diagnosis of RP demonstrating Coats-like exudative vitreoretinopathy between January 1, 2008, and October 1, 2019. METHODS: Evaluation of ocular findings at RP diagnosis and at time of presentation of Coats-like exudative vitreoretinopathy, pedigree analysis, genetic testing, retinal imaging, and anatomic outcomes after treatment. MAIN OUTCOME MEASURES: Visual acuity, ophthalmoscopy results, OCT results, fluorescein angiography results, and identification of genetic mutations. RESULTS: Nine patients diagnosed with RP and demonstrating Coats-like exudative vitreoretinopathy were included. Median age at time of RP diagnosis was 8 years (range, 1-22 years), and median age at presentation of Coats-like exudative vitreoretinopathy was 18 years (range, 1-41 years). Seven patients were female, and 2 were male. The genetic cause of disease was identified in 6 patients. Three patients demonstrated Coats-like fundus findings at the time of RP diagnosis. Exudative retinal detachment (ERD) localized to the infratemporal periphery was present in all patients, with bilateral disease observed in 7 patients. In all treated patients, focal laser photocoagulation was used to treat leaking telangiectasias and to limit further ERD expansion. Cystoid macular edema refractory to carbonic anhydrase inhibitor therapy and ultimately amenable to treatment with intravitreal anti-vascular endothelial growth factor injection was observed in 4 patients. CONCLUSIONS: Coats-like vitreoretinopathy is present in up to 5% of all RP patients. The term Coats-like RP is used colloquially to describe this disease state, which can present at the time of RP diagnosis or, more commonly, develops late during the clinical course of patients with longstanding RP. Coats-like RP is distinct from Coats disease in that exudative pathologic features occur exclusively in the setting of a coexisting RP diagnosis, is restricted to the infratemporal retina, can affect both eyes, and does not demonstrate a male gender bias. Given the risk of added vision loss posed by exudative vitreoretinopathy in patients with RP, a heightened awareness of this condition is critical in facilitating timely intervention.

Case Report: Effect of a Retinal Prosthesis System on Charles Bonnet Visual Hallucinations.

SIGNIFICANCE: Charles Bonnet syndrome is commonly encountered and diagnosed in low-vision patients. It can be distressing for some of them, as there is no known effective treatment of this condition. Although there is a growing interest in retinal implants for blind patients with severe retinal diseases, the effect of these devices on Charles Bonnet syndrome visual hallucinations remains undocumented. PURPOSE: The aim of this study was to report changes in the Charles Bonnet syndrome of a patient with retinitis pigmentosa after implantation of the Argus II retinal prosthesis. CASE REPORT: A 65-year-old patient with retinitis pigmentosa and no light perception was frequently experiencing Charles Bonnet syndrome. In the hope of improving his vision, he received an Argus II retinal prosthesis in 2018 and participated in a 10-week rehabilitation program at the Institut Nazareth et Louis-Braille. The nature and the frequency of his Charles Bonnet syndrome were documented with the Questionnaire de repérage du syndrome de Charles Bonnet (a French questionnaire used to screen for Charles Bonnet syndrome) before the surgery and for 70 weeks after it. The patient's visual acuity and visual fields were monitored during the same period. Additional tests were administered to document the visual, psychological, and cognitive states of the patient throughout the study. CONCLUSIONS: Although this case report confirmed that Argus II retinal prosthesis improves the performance of blind patients in visual tests, the improvement was not associated with a decrease in the symptoms of Charles Bonnet syndrome.

The Role of Telemedicine to Alleviate an Increasingly Burdened Healthcare System: Retinopathy of Prematurity.

Telemedicine-based remote digital fundus imaging (RDFI-TM) offers a promising platform for the screening of retinopathy of prematurity. RDFI-TM addresses some of the challenges faced by ophthalmologists in examining this vulnerable population in both low- and high-income countries. In this review, we studied the evidence on the use of RDFI-TM and analyzed the practical framework for RDFI-TM systems. We assessed the novel technological advances that can be deployed within RDFI-TM systems including noncontact imaging systems, smartphone-based imaging tools, and deep learning algorithms.