Addressing Technical Failures in a Diabetic Retinopathy Screening Program.

Purpose: Diabetic retinopathy (DR) is a preventable cause of blindness detectable through screening using retinal digital photography. The Irish National Diabetic Retina Screening (DRS) programme, Diabetic RetinaScreen, provides free screening services to patients with diabetes from aged 12 years and older. A technical failure (TF) occurs when digital retinal imaging is ungradable, resulting in delays in the diagnosis and treatment of sight-threatening disease. Despite their impact, the causes of TFs, and indeed the utility of interventions to prevent them, have not been extensively examined. Aim: Primary analysis aimed to identify factors associated with TF. Secondary analysis examined a subset of cases, assessing patient data from five time points between 2019 and 2021 to identify photographer/patient factors associated with TF. Methods: Patient data from the DRS database for one provider were extracted for analysis between 2018 and 2022. Information on patient demographics, screening results, and other factors previously associated with TF were analyzed. Primary analysis involved using mixed-effects logistic regression models with nested patient-eye random effects. Secondary analysis reviewed a subset of cases in detail, checking for causes of TF. Results: The primary analysis included a total of 366,528 appointments from 104,407 patients over 5 years. Most patients had Type 2 diabetes (89.2%), and the overall TF rate was 4.9%. Diabetes type and duration, dilate pupil status, and the presence of lens artefacts on the camera were significantly associated with TF. The Secondary analysis identified the primary cause of TF was found to be optically dense cataracts, accounting for over half of the TFs. Conclusion: This study provides insight into the causes of TF within the Irish DRS program, highlighting cataracts as the primary contributing factor. The identification of patient-level factors associated with TF facilitates appropriate interventions that can be put in place to improve patient outcomes and minimize delays in treatment and diagnosis.

The Role of the Ophthalmic Genetics Multidisciplinary Team in the Management of Inherited Retinal Degenerations-A Case-Based Review.

(1) Background: Inherited retinal degenertions are rare conditions which may have a dramatic impact on the daily life of those affected and how they interact with their environment. Coordination of clinical services via an ophthalmic genetics multidisciplinary team (OG-MDT) allows better efficiency of time and resources to reach diagnoses and facilitate patient needs. (2) Methods: This clinical case series was conducted by a retrospective review of patient records for patients enrolled in the Target 5000 programme and managed by the OG-MDT, at the Mater Hospital Dublin, Ireland (n = 865) (3) Results: Herein we describe clinical cases and how the use of the OG-MDT optimizes care for isolated and syndromic IRD pedigrees. (4) Conclusions: this paper demonstrates the benefits of an OG-MDT to patients with IRDs resulting in the holistic resolution of complex and syndromic cases. Furthermore, we demonstrate that this format can be adopted/developed by similar centres around the world, bringing with it the myriad benefits.

Additional measures of macular function beyond visual acuity.

PURPOSE: Visual function is a complex process in which external visual stimuli are interpreted. Patients with retinal diseases and prolonged follow-up times may experience changes in their visual function that are not detected by the standard visual acuity measure, as they are a result of other alterations in visual function. With the advancement of different methods to evaluate visual function, additional measurements have become available, and further standardization suggests that some methods may be promising for use in clinical trials or routine clinical practice. The objectives of this article are to review these additional measurements and to provide guidance on their application. METHODS: The Vision Academy's membership of international retinal disease experts reviewed the literature and developed consensus recommendations for the application of additional measures of visual function in routine clinical practice or clinical trials. RESULTS: Measures such as low-luminance visual acuity, contrast sensitivity, retinal fixation and microperimetry, and reading performance are measures which can complement visual acuity measurements to provide an assessment of overall visual function, including impact on patients' quality of life. Measures such as dark adaptation, color vision testing, binocular vision testing, visual recognition testing, and shape discrimination require further optimization and validation before they can be implemented in everyday clinical practice. CONCLUSION: Additional measurements of visual function may help identify patients who could benefit from earlier diagnosis, detection of disease progression, and therapeutic intervention. New and additional functional clinical trial endpoints are required to fully understand the early stages of macular disease, its progression, and the response to treatment.

Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review.

Purpose: Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive (AR) syndromic inherited retinal degenerations (IRDs) representing 50% of deaf-blindness. All subtypes include retinitis pigmentosa, sensorineural hearing loss, and vestibular abnormalities. Thorough phenotyping may facilitate genetic diagnosis and intervention. Here we report the clinical/genetic features of an Irish USH cohort. Methods: USH patients were selected from the Irish IRD registry (Target 5000). Patients were examined clinically (deep-phenotyping) and genetically using a 254 IRD-associated gene target capture sequencing panel, USH2A exon, and whole genome sequencing. Results: The study identified 145 patients (24.1% USH1 [n = 35], 73.8% USH2 [n = 107], 1.4% USH3 [n = 2], and 0.7% USH4 [n = 1]). A genetic diagnosis was reached in 82.1%, the majority (80.7%) being MYO7A or USH2A genotypes. Mean visual acuity and visual field (VF) were 0.47 ± 0.58 LogMAR and 31.3° ± 32.8°, respectively, at a mean age of 43 years. Legal blindness criteria were met in 40.7%. Cataract was present in 77.4%. ADGRV1 genotypes had the most VF loss, whereas USH2A patients had greater myopia and CDH23 had the most astigmatism. Variants absent from gnomAD non-Finnish Europeans and ClinVar represented more than 20% of the variants identified and were detected in ADGRV1, ARSG, CDH23, MYO7A, and USH2A. Conclusions: USH is a genetically diverse group of AR IRDs that have a profound impact on affected individuals and their families. The prevalence and phenotype/genotype characteristics of USH in Ireland have, as yet, gone unreported. Understanding the genotype of Irish USH patients may guide clinical and genetic characterization facilitating access to existing/novel therapeutics.

Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients.

Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Evaluating transformative health leadership education for Indigenous health: a mixed methods study.

BACKGROUND: There is an urgent need to improve structural competency and anti-racism education across health systems. Many leaders in health systems have the ability and responsibility to play a significant role in policy change and transforming healthcare delivery to address health inequities and injustices. The aim of this project was to evaluate a new health leadership Indigenous health course: PLUS4I. METHODS: A mixed methods design grounded in a pragmatic paradigm was used. Attendees to the first four cohorts (n=75) were sent an invitation to complete a survey evaluating their learning immediately after the completion of PLUS4I. We retrospectively collected self-efficacy ratings from participants who were also invited to participate in a semi-structured interview about their experience in PLUS4I. Descriptive statistical analysis was conducted for the quantitative assessment of the survey data. A qualitative descriptive approach to thematic analysis was used for the qualitative interview data. RESULTS: A total of 45 completed quantitative evaluations (n=45) were completed across all four cohorts. Paired t-tests were used to show pre-changes and post-changes in self-reported confidence on a 6-point Likert scale across four categories of activities. Improvements were seen in the ratings across all categories of activities, and all were statistically significant (p<0.001). Two overarching themes emerged from the qualitative analysis: breaking down previous knowledge and critical applications; building new knowledge and change-making competencies. The qualitative interviews (n=25) averaged 32:23 min, with 18 female (72%) and 7 male (28%) interview participants. CONCLUSION: Future work will support expansion of the PLUS4I course into other work environments and faculties, where the learning environment, structure and relevant Truth and Reconciliation Calls to Action may be different. This work responds to the urgent need to create systems-level change to address structural racism and implement high-quality Indigenous health and anti-racism education.

Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements.

BACKGROUND: The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4). AIMS: The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups. METHODS: A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements. RESULTS: We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance. CONCLUSION: The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD.

The Effect on Patients' Visual Acuity and Grade, Secondary to Non-Attendance at Treatment Centers, Post Referral from Diabetic RetinaScreen Ireland.

Background: Patient non-attendance following referral to hospital is a significant challenge, in particular, for persons with diabetes. Aim: We sought to determine the impact on both visual acuity and the subsequent follow-up retinopathy grade of patients when they fail to attend Diabetic Retinopathy Treatment (DRT) Centers following referral from Diabetic RetinaScreen (DRS). Methods: A retrospective analysis of patients discharged from DRT due to multiple consecutive missed appointments between January 2016 and June 2021. Patients discharged for non-attendance were compared with patients discharged from completed treatment. Results: Of the 24,945 NEC patients referred to DRT, 5900 (24%) and 9345 (37%) were discharged back to DRS due to non-attendance and completed treatment, respectively. Those discharged for non-attendance were younger (60.7 v 63.4, p < 0.001) and had higher proportions of males (67% v 63%, p < 0.001) and people with type 1 diabetes (27% v 18%, p < 0.001). After attending rescreening after discharge, those discharged for non-attendance were significantly more likely to have a worsening of DR grade (26% v 8%, p < 0.001). Conclusion: Despite being notified that further investigation (with possible treatment) was required post DRS, many diabetic patients failed to attend for further management of their eye care in DRT. These patients had worse visual outcomes compared to those that attended. Improved patient education and communication are required to mitigate against the consequences of non-attendance.

Intolerance of uncertainty, posttraumatic stress, depression, and fears for the future among displaced refugees.

INTRODUCTION: The vast majority of the 100 million forcibly displaced persons worldwide live in a state of prolonged uncertainty with limited resettlement prospects and access to resources. Little is known, however, regarding how refugees and asylum-seekers cope with this uncertainty. METHODS: In this study, we investigated the longitudinal association between a measure of how people cope with uncertainty (intolerance of uncertainty (IU)), fears for the future, posttraumatic stress disorder (PTSD) symptoms and depression symptoms. A sample of 1,237 refugees displaced in Indonesia completed an online survey in Arabic, Farsi, Dari, Somali or English at two time-points six-months apart. RESULTS: Results indicated that greater IU-inhibitory anxiety (IU-IA or impairment related to uncertainty) was associated with subsequent increases in PTSD and depression symptoms and fears for the future. Greater PTSD symptoms and fears for the future were associated with increases in IU-prospective anxiety (IU-PA or distress related to uncertainty), and greater depression symptoms were associated with increases in IU-IA. DISCUSSION: These findings provide evidence for the mechanistic role of IU in psychological symptoms amongst displaced refugees. Results underscore the importance of policies to reduce uncertainty in displacement environments, and highlight IU as a potential intervention target to help refugees cope with protracted displacement.

The impact of COVID-19 stressors on refugee mental health and well-being in the context of sustained displacement.

Refugees and asylum seekers in contexts of sustained displacement represent particularly vulnerable communities during the COVID-19 pandemic. The aim of this study was to identify profiles of COVID-19 stressors in refugees in a transit context (i.e., Indonesia) and examine the relationship between these profiles of stressors and mental health and well-being. Participants in this study included 913 refugees and asylum seekers living in Indonesia. The study was completed online in five languages (i.e., Arabic, Dari, Farsi, Somali, and English). A latent class analysis was implemented with 12 COVID-19 stressors representing indicator variables to identify profiles of COVID-19-related stressors experienced. Associations between COVID-19 classes and mental health (posttraumatic stress disorder, depression, anxiety) and well-being (physical and mental) outcomes were investigated. A five-class solution was identified as providing the best fit to the data as follows: (a) a high-COVID stressors class (18.1%), (b) a high access stressors class (13.2%), (c) an infection stressors class (22.7%), (d) a moderate access stressors class (23.1%), and (e) a low-COVID stressors class (22.8%). Membership of all classes reporting at least moderate levels of COVID-19 stressors was associated with greater mental health difficulties and lower physical and mental well-being than the low-COVID stressors class. Results indicated that the severity and type of stressors differed between groups suggesting heterogeneous experiences of the pandemic. Classes also differed according to contextual and social factors such as negative social support, language, and geographic area. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Subretinal fluid may protect against macular atrophy in neovascular age-related macular degeneration: 5 years of follow-up from Fight Retinal Blindness registry.

PURPOSE: The purpose of the study was to assess the association of macular atrophy (MA) according to the activity of macular neovascularization (MNV) (inactive, only subretinal fluid [SRFL], or active, i.e. including intraretinal fluid [IRFL]) using optical coherence tomography (OCT) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Multicentric observational study. Treatment-naïve nAMD eyes without subfoveal MA or subretinal fibrosis (SF) at baseline were included since 1st January 2010 and 30th September 2016 to allow up to 5 years of treatment follow-up. Eyes were grouped based on their predominant activity status as: (1) mostly inactive, (2) mostly active non-SRFL only [IRFL] or (3) mostly active-SRFL only [onlySRFL]. Kaplan-Meier survival curves estimated the time to development of MA or SF. Cox proportional hazards models evaluated predictors of developing subfoveal MA or SF. The main outcome measure was the risk of developing MA according to predominant MNV activity. RESULTS: A total of 973 eyes were eligible for analysis. OnlySRFL eyes had lower risk of developing subfoveal MA (HR [95% CI]: 0.56 [0.36, 0.88]; p = 0.024) and extrafoveal MA (HR [95% CI]: 0.41 [0.27, 0.61]; p < 0.001) than IRFL eyes. IRFL eyes had lower visual acuity (VA) (54.5 letters) and the highest proportion of eyes with vision ≤35 letters (25%) at 5 years while onlySRFL eyes had comparable 5-year VA (63.7 letters) to inactive eyes (63.7 letters). CONCLUSION: Subretinal fluid appears to protect against MA. Distinguishing the compartment of retinal fluid and understanding its relationship with MA and SF can guide the management of nAMD.

Serum MicroRNAs Profiling in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the retina which ultimately results in the irreversible loss of central vision. AMD is one of the foremost causes of blindness in people over the age of 50. Although the precise pathogenesis of AMD has not yet been elucidated, AMD results from a complex interaction between genetic predisposition and environmental provoking factors. These factors might lead to ocular homeostasis dysfunction resulting in inflammation, oxidative stress, and in some cases neovascularization. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs and are approximately 22 nucleotides long. miRNAs play a central role in several pathophysiological processes such as immune and inflammatory responses, pathological angiogenesis, and the response to oxidative stress, all of which have been suggested to be associated with AMD pathogenesis and progression. Here we discuss methods to isolate miRNAs using serum specimens from AMD patients and miRNA profiling for the better understanding of the pathogenesis and progression of AMD.

Context, coping, and mental health in refugees living in protracted displacement.

There is currently an unprecedented number of forcibly displaced people worldwide. Little is known, however, about how external stressors and internal coping strategies intersect to influence mental health in displaced refugees, particularly whether specific types of coping strategies are more or less effective across different levels of external stress. This study aimed to understand whether positive and negative internal coping strategies were differentially associated with mental health across high and low levels of external stressors in displaced refugees. Participants were 1,216 refugees living in Indonesia who completed an online survey indexing demographic characteristics, exposure to ongoing stressors, positive psychological coping strategies (i.e., cognitive flexibility, self-efficacy, and hope), negative psychological coping strategies (i.e., rumination and intolerance of uncertainty), psychological symptoms (i.e., posttraumatic stress disorder, depression, and anxiety) and mental health-related quality of life. Participants (27.3% female, Mage = 30.52 years) were from Arabic-, Farsi-, Tamil-, Somali-, Dari-, and English-speaking backgrounds. Results of latent moderated structural equation modeling indicated that the association between negative psychological coping strategies and poorer mental health was stronger at higher levels of stress, whereas the association between positive psychological coping strategies and better quality of life was stronger at lower levels of stress. These findings provide evidence in support of tailored approaches that integrate interventions addressing external stressors and internal coping strategies to support positive mental health and enhanced quality of life in displaced refugees.

Impact of displacement context on psychological distress in refugees resettled in Australia: a longitudinal population-based study.

AIMS: Refugees typically spend years in a state of protracted displacement prior to permanent resettlement. Little is known about how various prior displacement contexts influence long-term mental health in resettled refugees. In this study, we aimed to determine whether having lived in refugee camps v. community settings prior to resettlement impacted the course of refugees' psychological distress over the 4 years following arrival in Australia. METHODS: Participants were 1887 refugees who had taken part in the Building a New Life in Australia study, which comprised of five annual face-to-face or telephone surveys from the year of first arrival in Australia. RESULTS: Latent growth curve modelling revealed that refugees who had lived in camps showed greater initial psychological distress (as indexed by the K6) and faster decreases in psychological distress in the 4 years after resettling in Australia, compared to those who had lived in community settings. Investigation of refugee camp characteristics revealed that poorer access to services in camps was associated with greater initial distress after resettlement, and greater ability to meet one's basic needs in camps was associated with faster decreases in psychological distress over time. CONCLUSIONS: These findings highlight the importance of the displacement context in influencing the course of post-resettlement mental health. Increasing available services and meeting basic needs in the displacement environment may promote better mental health outcomes in resettled refugees.

Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population.

Inherited retinal degenerations (IRDs) account for over one third of the underlying causes of blindness in the paediatric population. Patients with IRDs often experience long delays prior to reaching a definitive diagnosis. Children attending a tertiary care paediatric ophthalmology department with phenotypic (i.e., clinical and/or electrophysiologic) evidence suggestive of IRD were contacted for genetic testing during the SARS-CoV-2-19 pandemic using a "telegenetics" approach. Genetic testing approach was panel-based next generation sequencing (351 genes) via a commercial laboratory (Blueprint Genetics, Helsinki, Finland). Of 70 patient samples from 57 pedigrees undergoing genetic testing, a causative genetic variant(s) was detected for 60 patients (85.7%) from 47 (82.5%) pedigrees. Of the 60 genetically resolved IRD patients, 5% (n = 3) are eligible for approved therapies (RPE65) and 38.3% (n = 23) are eligible for clinical trial-based gene therapies including CEP290 (n = 2), CNGA3 (n = 3), CNGB3 (n = 6), RPGR (n = 5) and RS1 (n = 7). The early introduction of genetic testing in the diagnostic/care pathway for children with IRDs is critical for genetic counselling of these families prior to upcoming gene therapy trials. Herein, we describe the pathway used, the clinical and genetic findings, and the therapeutic implications of the first systematic coordinated round of genetic testing of a paediatric IRD cohort in Ireland.

Usher syndrome type IV: clinically and molecularly confirmed by novel ARSG variants.

Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (ARSG) gene have been reported to underlie USH type IV. This distinct type of USH is characterized by late-onset RP with predominantly pericentral and macular changes, and late onset SNHL without vestibular dysfunction. In this study, we describe the USH type IV phenotype in three unrelated subjects. We identified three novel pathogenic variants, two novel likely pathogenic variants, and one previously described pathogenic variant in ARSG. Functional experiments indicated a loss of sulfatase activity of the mutant proteins. Our findings confirm that ARSG variants cause the newly defined USH type IV and support the proposed extension of the phenotypic USH classification.

Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing.

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70-80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.

Irish National Diabetic RetinaScreen Programme: report on five rounds of retinopathy screening and screen-positive referrals. (INDEAR study report no. 1).

OBJECTIVE: To study the uptake of annual diabetic retinopathy screening and study the 5-year trends in the detection of screen-positive diabetic retinopathy and non-diabetes-related eye disease in a cohort of annually screened individuals. DESIGN: Retrospective retinopathy screening attendance and retinopathy grading analysis. SETTING: Community-based retinopathy screening centres for the Diabetic RetinaScreen Programme. PARTICIPANTS: 171 557 were identified by the screening programme to be eligible for annual diabetic retinopathy screening. 120 048 individuals over the age of 12 consented to and attended at least one screening appointment between February 2013 to December 2018. MAIN OUTCOME MEASURES: Detection rate per 100 000 of any retinopathy, screen-positive referrable retinopathy and nondiabetic eye disease. RESULTS: Uptake of screening had reached 67.2% in the fifth round of screening. Detection rate of screen-positive retinopathy reduced from 13 229 to 4237 per 100 000 screened over five rounds. Detection of proliferative disease had reduced from 2898 to 713 per 100 000 screened. Non-diabetic eye disease detection and referral to treatment centres increased almost eightfold from 393 in round 1 to 3225 per 100 000 screened. The majority of individuals referred to treatment centres for ophthalmologist assessment are over the age of 50 years. CONCLUSIONS: Screening programme has seen a reduced detection rate both screen-positive retinopathy referral in Ireland over five rounds of screening. Management of nondiabetic eye diseases poses a significant challenge in improving visual outcomes of people living with diabetes in Ireland.

MFRP-Associated Retinopathy and Nanophthalmos in Two Irish Probands: A Case Report.

The conjunction of nanophthalmos (NO) and retinitis pigmentosa (RP) provides challenges to effective clinical management while narrowing the genetic spectrum for targeted molecular diagnostics. This case study describes two not knowingly related adult cases of MFRP-associated retinopathy and nanophthalmos (MARN). Structural features including short axial lengths (mean 16.4 mm), steep keratometry (mean 49.98 D), adult-onset signs, and symptoms of retinal dystrophy and acquired disease (i.e., cataract, angle-closure glaucoma) were evident in both cases. Pathogenic variants in the MFRP gene impair both prenatal eye growth and childhood emmetropization while also leading to RPE/outer retinal degeneration in 75% of cases. We discuss the "small-eye" phenotype spectrum and associated defining characteristics, molecular mechanisms with particular focus on MFRP-associated NO with RP features (MARN), the spectrum of visual morbidities (e.g., extreme refractive error, amblyopia, cystoid macular lesions, early cataract) and the challenges of their treatment/surgical management.