Ophthalmic Features Research Articles

Transformative applications of oculomics-based AI approaches in the management of systemic diseases: A systematic review.

Systemic diseases, such as cardiovascular and cerebrovascular conditions, pose significant global health challenges due to their high mortality rates. Early identification and intervention in systemic diseases can substantially enhance their prognosis. However, diagnosing systemic diseases often necessitates complex, expensive, and invasive tests, posing challenges in their timely detection. Therefore, simple, cost-effective, and non-invasive methods for the management (such as screening, diagnosis, and monitoring) of systemic diseases are needed to reduce associated comorbidities and mortality rates. This systematic review examines the application of artificial intelligence (AI) algorithms in managing systemic diseases by analyzing ophthalmic features (oculomics) obtained from convenient, affordable, and non-invasive ophthalmic imaging. Our analysis demonstrates the promising accuracy of AI in predicting systemic diseases. Subgroup analysis reveals promising capabilities of oculomics-based AI for disease staging, while caution is warranted due to the possible overestimation of AI capabilities in low-quality studies. These systems are cost-effective and safe, with high rates of acceptance among patients and clinicians. This review underscores the potential of oculomics-based AI approaches in revolutionizing the management of systemic diseases.

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or ‘wolframinopathies’, exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the ‘plus’ phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Spotlight on Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC).

Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC) is a rare syndrome caused by biallelic mutations in the JAM3 gene with significant intrafamilial variability in clinical presentation and brain imaging phenotypes. The clinical presentation of HDBSCC includes severe recurrent hemorrhages involving the brain parenchyma and the ventricles beginning in utero and continuing in infancy together with dense central cataracts present at birth. This comprehensive review documents reported cases on this unique condition and describes its genetic, neuroradiologic and ophthalmic features. It should be included in the differential diagnosis of children with congenital cataracts and neurodevelopmental abnormalities. Unique clinical, imaging findings and genetic testing can help the diagnosis.

Ocular Complications of Mpox: Evolving Understanding and Future Directions.

Mpox (formerly known as monkeypox), an infectious disease caused by the monkeypox virus (MPXV), has been endemic in regions of Central and Western Africa. In 2022, the global spread of the clade IIb MPXV led to a multinational outbreak, primarily affecting sexual transmission networks among men who have sex with men. Despite interventions, new cases have continued to emerge. In Africa, the spread of a novel strain of clade I MPXV, clade Ib, has prompted a Public Health Emergency of International Concern designation by the World Health Organization in August 2024. This article provides an updated overview of the epidemiology, systemic, and ocular manifestations, highlighting the clinical features, diagnostic testing, and implications relevant to ophthalmologists and eye care providers, including infection prevention and control measures. The ocular manifestations of mpox primarily involve the ocular surface and anterior segment, with presentations ranging from conjunctivitis to severe, vision-threatening keratitis and uveitis. While the 2022 to 2024 Clade IIb outbreak has shown a lower incidence of ocular involvement compared with previous outbreaks, the potential for significant visual morbidity remains. Treatment involves both systemic and topical therapies, with tecovirimat being the primary systemic option, though its efficacy and ophthalmic bioavailability remain under investigation. Ongoing surveillance and research are essential to further understand the epidemiology and ophthalmic features of mpox and, ultimately, to optimize prevention and treatment strategies for patients.

Sturge-Weber Syndrome: a case report

Sturge-Weber syndrome is a rare congenital, non-familial sporadic condition also known as encephalotrigeminal angiomatosis, is a phakomatoses consisting of neurological, skin and ocular manifestations. Symptoms reported varies in severity and age of onset but it is commonly detected in infancy. The Ophthalmic feature of this disease consists of glaucoma and is also associated with vascular manifestation of the conjunctiva, epi-sclera, choroid and retina. In the present case, a 19-year-old male presented with a port wine stain on the right side of the face, leptomeningeal angioma, ocular hypertension, temporal hemianopia of the left eye and choroidal hemangioma with macular scar of the right eye, seizure and weakness of the left side of the body. The purpose of presenting the case is to illustrate both the characteristic presentation and to underline the importance of its diagnosis in the clinical ophthalmological practice. BIRDEM Med J 2024; 14(3): 166-169

Severe Leukemic Retinopathy due to Acute Lymphoblastic leukemia

Leukaemia is a myeloproliferative disorder which commonly affects the eye. The retina is most commonly affected by leukaemia. Both acute and chronic leukaemia can develop retinopathy. Patients can develop anaemia and thrombocytopenia. The ophthalmic features include white-centred retinal haemorrhages (Roth spot), cotton wool spots, macular haemorrhages and vitreous haemorrhages. CNS involvement through the optic nerve can cause papillo-oedema and cranial nerve palsy. Opportunistic infection can occur after chemotherapy. A young female patient was diagnosed with Acute Lymphoblastic leukaemia (ALL); she presented with pain and blurred vision in both her eyes. In coloured fundus photograph (CFP) shows dilated, tortuous blood vessels and grey-white streaks along vessels due to perivascular infiltrate. Large whitish opacity all over the fundus. Optic nerve infiltration is also present. Vascular occlusion like CRVO occurs due to hyperviscosity. OCT shows leukaemic infiltration of the retina, causing detachment. The modalities of the Management of leukaemia involve chemotherapy, immunotherapy or radiotherapy, but the Management of leukaemic retinopathy is symptomatic. ALL is treated with vincristine, prednisolone and L-asparagine. Eye treatment was done by intravitreal injection of methotrexate. Patients with acute lymphoblastic leukaemia (ALL) may be asymptomatic and develop vision loss (VL). CBMJ 2024 July: vol. 13 no. 02 P: 277-281

Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas

PurposeTo determine whether microstructural retinal changes, tumor features, and Apolipoprotein E (APOE) ε4 polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas. DesignCohort study. Participants and ControlsSixteen lower-grade glioma patients at a U.S. academic Ophthalmology department between January 2021 and November 2023. Normal controls were recruited from convenient sampling. MethodsMontreal Cognitive Assessment (MoCA) scores and retinal changes were assessed in 6-months intervals. APOE genotyping was performed, and tumor details were recorded. Partial least-squares discriminant (PLSD) model was established to evaluate the association between TACD with APOE genotype, ophthalmic, and tumor features. Main Outcome MeasuresThe main outcome measure was cognitive status as measured by the MoCA score and analyzed in relation to ophthalmic measurements, tumor features, and APOE genotype. ResultsMedian time to first eye exam was 34 months (2–266) from tumor diagnosis and 23 months (0–246) from radiation. Nine patients (56%) had abnormal cognition (MoCA <26/30). MoCA scores were significantly worse in patients with temporal (22±7.2) than frontal lobe tumors (26±3.1, p=0.02) and those with oligodendrogliomas (22±4.1) than astrocytomas (26±3.6, =0.02). Patients with TACD had significant radial peripapillary capillary density loss (45%±4.6) compared to those with normal cognition (49%±2.6, p=0.02). A PLSD model correlated MoCA scores with retinal nerve fiber thickness, intraocular pressure, foveal avascular zone, best-corrected visual acuity, months since first diagnosis, and tumor pathology (oligodendroglioma or not). Using these features, the model identified patients with TACD with 77% accuracy. APOE genotyping showed: two ε2/ε3 (13%), ten ε3/ε3 (63%), and one ε3/ε4 (6%). ConclusionRetinal microstructural changes may serve as biomarkers for TACD in patients with lower-grade gliomas. Temporal lobe tumors and oligodendrogliomas may increase susceptibility to TACD. Utilization of retinal markers may enhance TACD diagnosis, progression monitoring, and inform management of lower-grade glioma patients. A larger study with serial eye exams is warranted to evaluate the role of APOE ε4 and develop a predictive model.

Development of oculomics artificial intelligence for cardiovascular risk factors: A case study in fundus oculomics for HbA1c assessment and clinically relevant considerations for clinicians

Artificial Intelligence (AI) is transforming healthcare, notably in ophthalmology, where its ability to interpret images and data can significantly enhance disease diagnosis and patient care. Recent developments in oculomics, the integration of ophthalmic features to develop biomarkers for systemic diseases, have demonstrated the potential for providing rapid, non-invasive methods of screening leading to enhance in early detection and improve healthcare quality, particularly in underserved areas. However, the widespread adoption of such AI-based technologies faces challenges primarily related to the trustworthiness of the system. We demonstrate the potential and considerations needed to develop trustworthy AI in oculomics through a pilot study for HbA1c assessment using an AI-based approach. We then discuss various challenges, considerations, and solutions that have been developed for powerful AI technologies in the past in healthcare and subsequently apply these considerations to the oculomics pilot study. Building upon the observations in the study we highlight the challenges and opportunities for advancing trustworthy AI in oculomics. Ultimately, oculomics presents as a powerful and emerging technology in ophthalmology and understanding how to optimize transparency prior to clinical adoption is of utmost importance.

Long-term visual outcomes in spasmus nutans

BackgroundThe long-term visual outcomes in spasmus nutans patients is largely unknown. The purpose of this study was to characterize visual outcomes and identify comorbid ophthalmic conditions in patients with spasmus nutans.MethodsWe retrospectively reviewed the charts of consecutive patients diagnosed with spasmus nutans between 2000 and 2020. Demographic information, ophthalmic characteristics, and neuroimaging results were assessed over time.ResultsOf the 32 patients included in the study, 13 (41%) were female. Underlying medical conditions included a diagnosis of Trisomy 21 in 6 (19%) and prematurity in 8 (25%). Twenty-one patients (66%) self-reported as a race other than Caucasian. 18 patients (56%) had non-private health insurance and 1 (3%) was uninsured. Mean age at diagnosis and resolution were 16 months (range 45 months) and 48 months (range 114 months), respectively. All 32 patients had nystagmus, 31 (97%) had head nodding and 16 (50%) had ocular torticollis. Mean follow-up was 66 months (range 185 months). On initial presentation, 6/32 (19%) had an amblyogenic refractive error and mean best-corrected visual acuity (BCVA) in the better-seeing eye was 0.78 Logarithm of the Minimum Angle of Resolution (LogMAR) (range 1.24). In a sub-analysis that included patients with > 1 exam (n = 23), 17/20 (85%) had an amblyogenic refractive error and mean BCVA in the better-seeing eye was 0.48 LogMAR (range 1.70). At the final exam, 12 patients had measurable stereopsis, eight had strabismus, and three had undergone strabismus surgery. Eight patients required treatment for amblyopia.ConclusionsWe found a high prevalence of amblyogenic refractive error, strabismus and amblyopia among patients with spasmus nutans. Children with spasmus nutans benefit from ongoing ophthalmic follow-up until they are past the amblyopic age range, even after resolution of nystagmus.

Clinical characteristics of recurrent non-arteritic retinal artery occlusion

ObjectivesTo investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye.MethodsWe searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent...

A Beginner's Guide to Artificial Intelligence for Ophthalmologists.

The integration of artificial intelligence (AI) in ophthalmology has promoted the development of the discipline, offering opportunities for enhancing diagnostic accuracy, patient care, and treatment outcomes. This paper aims to provide a foundational understanding of AI applications in ophthalmology, with a focus on interpreting studies related to AI-driven diagnostics. The core of our discussion is to explore various AI methods, including deep learning (DL) frameworks for detecting and quantifying ophthalmic features in imaging data, as well as using transfer learning for effective model training in limited datasets. The paper highlights the importance of high-quality, diverse datasets for training AI models and the need for transparent reporting of methodologies to ensure reproducibility and reliability in AI studies. Furthermore, we address the clinical implications of AI diagnostics, emphasizing the balance between minimizing false negatives to avoid missed diagnoses and reducing false positives to prevent unnecessary interventions. The paper also discusses the ethical considerations and potential biases in AI models, underscoring the importance of continuous monitoring and improvement of AI systems in clinical settings. In conclusion, this paper serves as a primer for ophthalmologists seeking to understand the basics of AI in their field, guiding them through the critical aspects of interpreting AI studies and the practical considerations for integrating AI into clinical practice.

The Effectiveness of Facial Exercise Therapy in Ophthalmic Complications of Facial Nerve Palsy and the CADS Grading Scale as an Ophthalmic-Specific Grading System.

The effectiveness of facial exercise therapy in facial nerve palsy is well documented in the literature. However, there is no study examining its effect on ophthalmic manifestations of facial nerve palsy. The study reports its impact on the ophthalmic manifestations of facial nerve palsy using the ophthalmic-specific CADS grading system. A retrospective case series of patients aged 18 years or older with facial nerve palsy was performed in a single specialist center between 2013 and 2019. Inclusion criteria were ophthalmic involvement, recorded CADS, and Sunnybrook grading scale pre- and post-treatment. A total of 73 patients were identified. There were 24 patients (M = 11, F = 13) who received facial exercise therapy only (group 1) and 49 patients (M = 17, F = 32) who received combined treatment of facial exercise therapy and eyelid surgery (group 2). The mean ages were 54.8 and 49.7 years, respectively. The groups were further subdivided into early (<3 months), intermediate (3-12 months), and late presenters (>12 months). In group 1, statistically significant improvements were seen in early (static asymmetry and dynamic function), intermediate (cornea), and late groups (cornea, static asymmetry, and dynamic function). The Sunnybrook grading scale was unable to detect changes in the ophthalmic features post-therapy or to report the corneal status. Facial exercise therapy is likely to improve ophthalmic manifestations of facial nerve palsy, in particular, those with static asymmetry and dynamic function of eye closure. The CADS grading scale is more suitable for the ophthalmic assessment.

E078 Long term outcomes of diffuse alveolar haemorrhage in antineutrophil cytoplasmic antibody-associated vasculitis: a single centre study

Abstract Background/Aims ANCA associated vasculitis (AAV) is a heterogeneous disease with significant mortality and morbidity. Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition and presents with hemoptysis, cough, breathlessness and respiratory failure. Studies have shown a prevalence of about 25%. This study was designed to assess the clinical features, serology, efficacy of treatment and long term outcomes in DAH patients secondary to AAV. Methods This was an observational study which included adult AAV Patients diagnosed based on Revised International Chapel Hill Consensus Conference classification criteria from January 2016 to August, 2023 after IEC approval. DAH was diagnosed based on clinical symptoms, Imaging (Diffuse alveolar infiltrates), drop in hemoglobin, hypoxia and Bronchoalveolar lavage in cases where feasible. Demographic details, clinical features, laboratory data including ANCA serology, treatment, disease activity, outcomes of patients were assessed prospectively. DAH and Non DAH groups were compared using Kruskal Wallis test for median values. Student t-test for mean values and Chi square for categorical variables were used to test association between two groups with statistical significance of P-Value &amp;lt;0.05. Results 133 AAV patients were included in the study. DAH was seen in 42(31.5%) patients. The mean (± SD) age of patients was 49.4(±18.9) years. Males (52.3%) were marginally higher in number then females (47.6%). Patients presented with a median of 8 weeks after AAV diagnosis. Hemoptysis (61.9%), cough (47.6%) and breathlessness(64.3%) were the presenting complaints. Renal, Sinusitis, Gastrointestinal involvement was seen in 83.3%, 61.9% and 14.2% respectively. Musculoskeletal and Ophthalmic features were seen in 33.3% each. RPRF was seen in 42.8%. c-ANCA, p-ANCA were seen in 73.8%,21.4% while Anti PR3 antibody and Anti MPO antibody were seen in 78.5%, 21.4% patients respectively. Median (IQR) BVAS score at presentation was 20(13-24) compared to 11(7-11) in Non DAH group which was statistically significant (p &amp;lt; 0.001). 10(23.8%) patients required ventilator support. IVIg was given in 3(7.1%), while plasmapheresis was used in 7(16.7%). Induction regimen with Cyclophosphamide was used in 73.8% and Rituximab (RTX) in 8(19%) patients. Maintenance RTX was used in 42.8% and 45.2% patients received Azathioprine. 23.8% patients relapsed and 54.6% patients were in remission. 10(23.8%) required Mechanical Ventilation. No patients were on long term oxygen therapy. 7(16.6%) patients died. Morbidity was seen in 16(38%) including CKD in 8(19%) patients. Median(IQR) duration of follow up was 10(6-24) months. Conclusion DAH is a serious manifestation of AAV and an important Rheumatological emergency. DAH was present in 31.5% with majority patients in remission. Mortality was seen in 16.6% and morbidity in 38% cases. Management with combination of Pulse steroids, Cyclophosphamide /Rituximab and Plasmapheresis is the key to better outcomes. Ventilator support may be necessary in severe cases. Timely diagnosis and aggressive management is the key to survival and prevents morbidity. Disclosure J.R. Yadavalli: None. K. Telang: None. P. Khatri: None. S. Dhuria: None. G. Ekbote: None. R. Gupta: None.

A Novel Pathogenic Variant of the PRPH2 Gene in Multifocal Pattern Dystrophy Simulating Stargardt Disease: A Case Report and Major Review

Purpose: To present a novel pathogenic variant in PRPH2 in a patient with multifocal pattern dystrophy simulating Stargardt Disease (MPDsSD) and provide a review of the literature summarizing the clinical findings of all presented cases of MPDsSD. Methods: We performed a systematic review of the literature to summarize the clinical findings in patients with MPDsSD. A PubMed search of “(multifocal pattern dystrophy simulating stargardt disease) OR (multifocal pattern dystrophy simulating fundus flavimaculatus) OR (PRPH2 associated retinal dystrophy)” retrieved a total of 152 articles on April 2023. Articles describing the clinical and ophthalmic characteristics of patients with MPDsSD were included. We also describe the case of a 42-year-old male presenting to the clinic with blurry vision and progressively worsening vision in both eyes who was found to have a novel pathogenic variant in the PRPH2 gene. Results: Genetic testing revealed a pathogenic variant in PRPH2, c.640T&gt;C [p.(Cys214Arg)], which provided molecular confirmation of MPDsSD. Moreover, the systematic review, revealed 28 previously reported cases of MPDsSD. The most common presenting symptom among all patients was metamorphopsia (33% of cases). The most common finding on fundus exam was the presence of yellowish fleck-like deposits found in the posterior pole of the retina (83%). All cases of MPDsSD had hyper-autofluorescence of the yellow flecks on fundus autofluorescence. The mean age of onset was 41 years (28 – 65). Mean best corrected visual acuity (BCVA) at presentation was 0.27 (20/37) right eye (OD) and 0.26 (20/36) left eye (OS). Only 48% of the cases reported a known family history of PD. Conclusion: Molecular confirmation can help confirm a clinical suspicion of MPDsSD, as this condition may have overlapping features of other macular dystrophies, most notably Stargardt Disease.

Exploring Knobloch syndrome: A case series of two Indian families and a review of literature

This case series describes the clinical features and genetic testing results of four patients from two families affected by Knobloch syndrome (KS). KS is an autosomal recessive collagenopathy characterized by vitreoretinal degeneration, high myopia, retinal detachment, and occipital encephalocele. In addition, a myriad of other ophthalmic and systemic features may be present in the affected individuals. Mutations in the COL18A1 gene are primarily implicated in the pathogenesis of the disease. The phenotypical differences seen in our genetically-proven patients show the clinical heterogeneity of this condition. Diagnosis of KS type-1 was confirmed by genetic analysis in all affected patients. Surgical intervention was done to salvage vision in three patients. This case series highlights the importance of meticulous clinical examination and diagnosis of this rare condition. Genetic counseling and testing are important for suspected patients and for guiding patients on the visual prognosis of the disease.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Abstract&#x0D; Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial

PurposeWe describe the baseline ophthalmic and cardiovascular (CV) risk factors, reported as associated with NAION, across countries, race and sex for the Quark207 treatment trial for acute NAION. DesignProspective randomized control clinical trial ParticipantsAdults age 50-80 years old with acute NAION recruited from 80 sites across 8 countries, 191 of whom were controls.Main measuresOphthalmic features of NAION and CV risk factors MethodsWe evaluated demographics, clinical and ophthalmological data including best-corrected visual acuity (BCVA) and average visual field total deviation (TD) in affected eyes and cup:disc ratio in fellow eyes at enrollment. We report the prevalence (median and interquartile Q1, Q3) of ophthalmic features and CV risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn’s test with Bonferroni correction for continuous variables and Chi-square testing with Holm-Bonferroni correction for categorical variables. ResultsThe study enrolled 500 males and 229 females, median age 60 and 61 (p=0.027) years, respectively. Participants were predominantly White (570) and Asian (149). The study eye BCVA was 71 (53, 84) characters (approximately logMAR score 0.4), and the TD for stimulus III was -16.5 dB (-22.2, -12.6) and -15.7 dB (-20.8, -10.9) for stimulus V. The vertical and horizontal cup:disc ratio was 0.1 (0.1, 0.3) for unaffected fellow eyes. The prevalence of CV risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmological features, which differed between the Asian and White races. Males and females differed with respect to a few clinically meaningful features. ConclusionsThe CV risk factors in our NAION cohort varied among the seven countries, race and sex but were not typically more prevalent than previously reported in the general population. Ophthalmic features, typical of NAION, were generally consistent across countries, race and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice women. Having a small cup:disc ratio in the fellow eye was the most prevalent and consistent risk factor across all demographics. This study suggests that other factors, not yet identified, may contribute to the development of NAION.

Ophthalmic and Neuroimaging Associations In Optic Nerve Hypoplasia/Septo-Optic-Pituitary Dysplasia.

Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are neurodevelopmental disorders associated with congenital visual impairment. Our aim was to investigate associations between several ophthalmic and neuroimaging features in patients with ONH/SOD. A retrospective chart and neuroimaging review was performed in patients with ONH/SOD. Ophthalmic signs (e.g., monocular best-corrected visual acuity [BCVA], nystagmus, and strabismus) and neuroimaging data were extracted and their associations were investigated. There were 128 patients (70 males) with ONH/SOD who had neuroimaging. Their mean age at the end of the study was 13.2 (SD: 7.5) years. Ophthalmic data were available on 102 patients (58 males). BCVA varied from normal to no light perception. There were statistically significant associations between: (A) Reduced optic nerve or chiasm size on neuroimaging and more severely impaired BCVA and (B) laterality of the reduced optic nerve or chiasm size on neuroimaging and laterality of: (1) The eye with reduced BCVA, (2) small optic disc size, and (3) RAPD, if present (p ≤ 0.0002 each). The presence of symmetrically small optic nerves on MRI was significantly more common in patients with nystagmus than when nystagmus was absent (N = 96, 75% vs. 38.6%, p < 0.0001). The presence of neuronal migration disorders, their type and laterality were not associated with BCVA and laterality of the reduced BCVA. The functional and structural associations in ONH are consistent with the impaired visual function that results from the hypoplastic anterior visual pathways. However, these associations were not perfectly concordant making prediction of adult BCVA challenging in these patients.

TYR mutation in a Chinese population with oculocutaneous albinism: Molecular characteristics and ophthalmic manifestations

Oculocutaneous albinism (OCA) is a rare inherited disorder characterized by a partial or complete reduction of melanin biosynthesis that leads to hypopigmentation in the skin, hair and eyes. The OCA1 subtype is caused by mutations in TYR. The purpose of this study was to investigate the genetic and clinical ophthalmic characteristics of TYR mutations in patients with OCA. Herein, 51 probands with a clinical diagnosis of OCA were enrolled. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Overall, TYR mutations were detected in 37.3% (19/51) in the patients with OCA. Fifteen patients had compound heterozygous variants, and four cases had homozygous variants. Eleven different pathogenic variants in TYR were detected in these 19 patients, with missense, insertion, delins and nonsense in 71.1% (27/38), 15.8% (6/38), 2.6% (1/38), and 10.5% (4/38), respectively. Clinical examinations revealed that 84.2% (16/19) of patients were OCA1A, and 15.8% (3/19) were OCA1B. Most TYR probands (52.6%, 10/19) had moderate vision impairment, 15.8% (3/19) had severe visual impairment, 10.5% (2/19) exhibited blindness, only 5.3% (1/19) had mild visual impairment and 15.8% (3/19) were not available. Photophobia and nystagmus were found in 100% (19/19) of the patients. In addition, grade 4 foveal hypoplasia was detected in 100% (12/12) of the patients. In conclusion: The TYR patients exhibited severe ocular phenotypes: the majority (93.8%, 15/16) of them had a moderate vision impairment or worse, and 100% (12/12) had severe grade 4 foveal hypoplasia. These novel findings could provide insight into the understanding of OCA.