Comparison of The Results of Sponsored Genetic Testing Panels for Inherited Retinal Diseases.

Background/Objectives: Gene therapy's emergence has made molecular diagnosis for inherited retinal diseases clinically significant. Free genetic testing panels have improved testing access in clinical practice, yet the interpretation of results, especially variants of unknown significance (VUS), remains challenging and requires expertise. This study shares our experience in utilizing sponsored IRD panel tests by Invitae and Blueprint Genetics (BG), reporting their positivity rates, and comparing their reclassification of variants through amendments. Methods: This retrospective study analyzed genetic test reports from patients who underwent testing via Invitae or BG panels. A positive test was determined if there was a pathogenic mutation in an autosomal dominant gene, two pathogenic mutations in an autosomal recessive gene, or a pathogenic mutation in an X-linked gene in a male patient. Results: The testing positivity rates were 34.9% for Invitae (n = 109) and 42.1% for BG (n = 107). Invitae had more pathogenic variants per report (0.87 vs. 0.58 variants, p = 0.0038) and issued more amendments than BG (0.54 vs. 0.03 amendments; p < 0.01). Of the Invitae variant classification changes, 66.2% switched a VUS to benign. In the BG group, 75% of variant reclassifications changed a VUS to pathogenic. As a result of the Invitae amendments, 88% did not change the overall report result. Conclusions: While free-of-charge genetic testing panels offer valuable insights for diagnosing IRD, limitations such as low diagnostic yield and variant classification discrepancies persist between Invitae and BG. VUS should not be considered pathogenic in the clinical decision-making process. Careful interpretation of genetic testing is required.

Phthisical eye and orbital ischemia after cosmetic platelet-rich plasma injection to the forehead.

Purpose: To report a case of retrograde embolism of cosmetic injection of platelet-rich plasma (PRP) to the ophthalmic artery, resulting in orbital ischemia, blindness, and eventual phthisis bulbi. Observations: A 37-year-old woman presented with two days of vision loss OS beginning seconds after undergoing cosmetic PRP filler injections to the face at an outside clinic. Immediately after injection to the left medial forehead, the patient reported bleeding, transient loss of consciousness, and complete vision loss OS. Two days later, vision remained no light perception OS and she exhibited manifestations of both anterior and posterior segment ischemia in the left eye. These findings were ultimately attributed to retrograde embolism to the ophthalmic artery via inadvertent injection of PRP into the supratrochlear or supraorbital arteries. She ultimately did not regain her vision in the left eye and the eye became enophthalmic and phthisical. Conclusions: After conducting a literature review on August 18, 2023, utilizing PubMed and Google Scholar, and searching for the key words "platelet-rich plasma" and "vision loss" or "vision impairment," we did not find any prior reports of anterior segment ischemia or pan-orbital ischemia resulting in phthisis bulbi. In the setting of vision changes after cosmetic platelet-rich plasma filler injection. Additionally, there is no validated therapy for ophthalmic artery occlusion from any cosmetic filler embolism. Further research should prioritize developing therapeutic guidelines for managing such complications. Injectors should also be educated to emergently refer patients to hospitals with ophthalmology consults available and stroke protocols in place.

Biometric Risk Factors for Angle Closure Progression After Laser Peripheral Iridotomy.

Importance: Laser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI. Objective: To elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI. Design, Setting, and Participants: This was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022. Main Outcome and Measure: Six-year progression to PAC or AAC. Results: Cohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 µm (TISA at 500 µm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 µm (HR, 1.33 per 0.01 mm2 smaller; 95% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 µm ≤0.05 mm2; HR, 9.41; 95% CI, 3.39-26.08; P <.001) or gonioscopy (cumulative score ≤6; HR, 2.80; 95% CI, 1.13-6.93; P =.04) conferred higher risk of progression. Conclusions and Relevance: Study results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.

Prevalence and Risk Factors of Major Depression in Patients with Diabetic Retinopathy in a Nationally Representative Survey.

PURPOSE: Evaluate the prevalence and risk factors of depression in diabetic retinopathy (DR). Compare subjective and objective measures of visual function predictivity of depression. METHODS: National Health and Nutrition Examination Survey 2005-2008 participants aged ≥40 who underwent fundus photography, Patient Health Questionnaire (PHQ)-9, and Visual Function Questionnaire (VFQ-25) were included in the study. Multivariable logistic regression was used to evaluate whether DR was a significant risk factor for depression and to evaluate the risk factors for depression in those with DR. RESULTS: A total of 5704 participants, 47% male, and mean age 56.5 years were included in this study. Persons with moderate, severe non-proliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR) had higher prevalence of depression than participants with mild retinopathy or no retinopathy (14.3%, 6.9%, 7.0%). Moderate-to-severe NPDR or PDR (OR: 2.36, p = .04) was associated with depression. Among persons with DR, best-corrected visual acuity and HbA1c were not associated with depression. However, self-reported measures of vision were associated with depression: some of the time spent worrying about eyesight (OR: 4.59, p = .010), vision limit activities some of the time (OR: 8.52, p < .001), vision limits activities most/all of the time (OR: 6.99, p < .001). CONCLUSIONS: A significant proportion of patients with DR in the NHANES population had co-morbid major depression. Best corrected visual acuity was not associated with depression in those with DR, while subjective, self-reported measures were associated with depression, suggesting subjective measures are a better determinant of poor mood and low functional status.

Impact of Intraoperative Ocular Lubricants on Corneal Debridement Rate During Vitreoretinal Surgery.

PURPOSE: To compare surgical parameters among patients receiving Viscoat (sodium chondroitin sulfate 4%-sodium hyaluronate 3%) or Goniosol (hydroxypropyl methylcellulose 2.5%) as topical lubricants for retinal surgery. METHODS: This was a retrospective analysis of patients undergoing retinal surgery between March 2013 and March 2018 using Goniosol or Viscoat as adjuvants. Primary outcome measures were rate of corneal debridement and operative time between groups, compared using χ 2 and t-tests, respectively. RESULTS: Compared to Viscoat (n=319), the Goniosol group (n=210) had more frequent intraoperative corneal debridement (21.4% vs 0, p<0.05) and longer surgical times (98 vs 78 minutes, p<0.05). Patients in the Viscoat group had higher rates of complex procedures (34.8% vs 26.7%, p<0.05), but were younger (50.7 vs 55.0 years, p<0.05) and more likely to be phakic (83.4% vs 70.5%, p<0.05). CONCLUSION: These findings suggest potential advantages of using Viscoat over Goniosol for corneal lubrication to aid visualization during vitreoretinal surgery.

Association of Retinopathy and Insulin Resistance: NHANES 2005-2008.

Purpose: In animal models, insulin resistance without severe hyperglycemia is associated with retinopathy; however, corroborating data in humans are lacking. This study aims to investigate the prevalence of retinopathy in a population without diabetes and evaluate the association of insulin resistance and retinopathy within this group.Methods: The study population included 1914 adults age ≥40 without diabetes who were assigned to the morning, fasted group in the National Health and Nutrition Examination Survey 2005-2008, conducted by the Centers for Disease Control. Retinopathy was determined using fundus photos independently graded by a reading center and insulin resistance was determined using the homeostatic model of insulin resistance.Results: Prevalence of retinopathy in those without diabetes was survey design adjusted 9.4% (174/1914). In multivariable analyses, retinopathy was associated with insulin resistance (HOMA-IR OR: 1.09, 95% CI: 1.03, 1.16; p = .0030), male gender (OR: 1.39, 95% CI: 1.04, 1.85; p = .0267), and age (OR: 1.03, 95% CI: 1.01, 1.05; p = .0203).Conclusions: Insulin resistance in the absence of overt hyperglycemia could be an early driver of retinopathy.

Visual Field Loss in Patients With Diabetes in the Absence of Clinically-Detectable Vascular Retinopathy in a Nationally Representative Survey.

Purpose: Neuroretinopathy is increasingly being recognized as an independent cause of vision loss in diabetes. Visual field loss, as detected by frequency doubling technology (FDT)-based visual perimetry, is a sign of neuroretinopathy and occurs in early stages of diabetic retinopathy (DR). Here, we hypothesized that FDT visual field testing could identify patients with diabetic neuroretinopathy in the absence of clinically detectable microvascular DR. Methods: All National Health and Nutrition Examination Survey (NHANES) 2005-2008 participants receiving fundus photography and visual field screening by FDT were included in this study. Participants with self-reported glaucoma, use of glaucoma medications, or determination of glaucoma based on disk features were excluded. Visual fields were screened using FDT protocol in which participants underwent a 19-subfield suprathreshold test. Results: Patients with diabetes but no DR were more likely to have ≥1 subfield defects at 5%, 2%, and 1% probability levels than patients without diabetes (41.3% vs. 28.6%; 27.4% vs. 17.5%; 15.9% vs. 9.4%; all P < 0.0008). Multivariable regression showed that each additional glycated hemoglobin % (HbA1c) was associated with 19% greater odds of having ≥1 visual subfield defects in those with diabetes without DR (odds ratio: 1.19, 95% confidence interval: 1.07-1.33; P = 0.0020). Conclusions: Patients with diabetes have visual field defects in the absence of clinically detectable DR, suggesting neuroretinopathy precedes classical microvascular disease. These defects become more frequent with the onset of visible retinopathy and worsen as the retinopathy becomes more severe. Longitudinal studies are required to understand the pathogenesis of diabetic neuroretinopathy in relation to classic DR.

Complete Posterior Vitreous Detachment Reduces the Need for Treatment of Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the vitreomacular interface and its relation to treatment burden for diabetic macular edema (DME) in patients without overt vitreomacular traction (VMT). PATIENTS AND METHODS: A retrospective cohort study of 494 eyes from 274 patients who had macular spectral-domain optical coherence tomography (SD-OCT) and did not have proliferative diabetic retinopathy, DME, or VMT at the initial visit. Posterior vitreous detachment (PVD) was categorized at the initial visit into five stages (0-4) using SD-OCT parameters alone. RESULTS: Two of 34 eyes (6.9%) presenting with a complete PVD required DME treatment during follow-up, whereas 144 of 460 eyes (31.3%) without a complete PVD at baseline required treatment (P = .001, Chi-squared). After adjusting for age, ethnicity, gender, and HbA1c, complete PVD at baseline was associated with a significant reduction in risk of DME therapy (hazard ratio: 0.18; 95% confidence interval, 0.05-0.73; P = .02). CONCLUSION: Complete PVD is independently associated with a reduced need for DME treatment. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e266-e273.].

Muscle relaxant induced pancreatitis leading to hyperosmolar hyperglycemic state.

Muscle relaxants are commonly prescribed in the United States but may have deleterious side effects that are unrecognized by physicians. Here, we report a 55-year-old Caucasian man who developed pancreatitis and a subsequent hyperosmolar hyperglycemic state after being prescribed tizanidine. The patient had untreated hypertriglyceridemia, unbeknownst to the prescribing physician. While hypertriglyceridemia is a widely understood risk factor for pancreatitis, its incidence with tizanidine is not. As an alpha-2 agonist, tizanidine slows gastrointestinal motility by inhibiting gastrointestinal smooth muscle contraction, which could lead to ileus which occurred in this patient. Alpha-2 agonists further contract the hepato-pancreatic sphincter, which may result in obstruction of pancreatic enzyme flow via the pancreatic duct. This patient's case of pancreatitis was precipitated by 2 factors: (i) his use of tizanidine and (ii) hypertriglyceridemia. This case demonstrates that patients presenting with severe hypertriglyceridemia, or other potential risk factors for pancreatitis, should not be prescribed tizanidine.

Mistaken Identity: Missed Diagnosis of Type 1 Diabetes in an Older Adult.

Type 1 diabetes can occur at any age from infancy to elderhood. Patients with hyperglycemia onset at older ages are presumed to have type 2 diabetes, but the misdiagnosis of type 2 diabetes as type 1 diabetes in adults has serious consequences. Medical error in this domain leads to significant patient harm that could be avoided with the correct diagnostic testing. Here, we discuss the case of a 58-year-old man who presented with diabetic ketoacidosis (DKA) at age 51 but was given the diagnosis of type 2 diabetes. During two subsequent admissions for DKA, he suffered severe complications. After his third episode of DKA, antibodies and C-peptide were checked, prompting a change in diagnosis to T1DM. Following a correct diagnosis of T1DM, diabetes education and appropriate treatment, the patient remained free of DKA and had improved glucose control. Under-diagnosis of type 1 diabetes can lead to recurrence of life-threatening episodes of DKA. Anti-GAD antibody and C-peptide testing are under-utilized in the differential diagnosis of type 1 versus type 2 diabetes in adults. This case demonstrates the consequences of the mis-diagnosis of type 1 diabetes as type 2 diabetes. The correct diagnosis is necessary to prevent hospital readmissions, morbidity, mortality and medical errors.

High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database.

BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS: Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS: The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS: Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.

Late-Onset T1DM and Older Age Predict Risk of Additional Autoimmune Disease.

OBJECTIVE: Type 1 diabetes (T1DM) is associated with other autoimmune diseases (AIDs), which may have serious health consequences. The epidemiology of AIDs in T1DM is not well defined in adults with T1DM. In this cross-sectional cohort study, we sought to characterize the incident ages and prevalence of AIDs in adults with T1DM across a wide age spectrum. RESEARCH DESIGN AND METHODS: A total of 1,212 adults seen at the Washington University Diabetes Center from 2011 to 2018 provided informed consent for the collection of their age, sex, race, and disease onset data. We performed paired association analyses based on age at onset of T1DM. Multivariate logistic regression was used to evaluate the independent effects of sex, race, T1DM age of onset, and T1DM duration on the prevalence of an additional AID. RESULTS: Mean ± SD age of T1DM onset was 21.2 ± 14.4 years. AID incidence and prevalence increased with age. Female sex strongly predicted AID risk. The most prevalent T1DM-associated AIDs were thyroid disease, collagen vascular diseases, and pernicious anemia. T1DM age of onset and T1DM duration predicted AID risk. Patients with late-onset T1DM after 30 years of age had higher risks of developing additional AIDs compared with patients with younger T1DM onset. CONCLUSIONS: The prevalence of AIDs in patients with T1DM increases with age and female sex. Later onset of T1DM is an independent and significant risk factor for developing additional AIDs. Individuals who are diagnosed with T1DM at older ages, particularly women, should be monitored for other autoimmune conditions.

High prevalence of systemic rheumatic diseases in women with type 1 diabetes.

BACKGROUND: The prevalence of systemic rheumatic diseases (SRDs) in T1DM has not been described. METHOD: This observational study compares SRD prevalence across age, race, and gender in 1,212 adults with T1DM. FINDINGS: There is an age-dependent enrichment of SRDs in women with T1DM: 9.2% prevalence in women overall and 14% in women over age 50. CONCLUSION: Clinicians taking care of older women with T1DM should monitor for these SRDs.

Bilateral Lower Extremity Paralysis in a Caucasian Male Presenting to the Emergency Department.

Reported is a case of a 39-year-old Caucasian man who presented to the emergency department with sudden onset bilateral lower extremity paralysis after consuming a large amount of carbohydrates and alcohol. A CT, MRI, and lumbar puncture were performed with negative results; lab results showed hyperthyroidism and hypokalemia. The patient was diagnosed with thyrotoxic periodic paralysis. In a patient presenting with sudden onset paralysis and hypokalemia, the emergency physician should include thyrotoxic periodic paralysis in the differential diagnosis and focus on treating and working up the hypokalemia instead of the paralysis.