RETINAL MANIFESTATIONS OF WALKER-WARBURG SYNDROME IN TWO SIBLINGS WITH RXYLT1 MUTATIONS.

PURPOSE: We report two siblings with genetically confirmed Walker-Warburg syndrome (WWS), studied with multimodal imaging, who presented with different retinal manifestations. METHODS: This is a retrospective report of two WWS cases with ultra-widefield fundus photography, fluorescein angiography, and ultrasound. Molecular diagnosis was achieved using panel testing and targeted variant testing. RESULTS: Two siblings, one male and one female, born 17 months apart with a diagnosis of WWS underwent retinal examination with imaging. The 3-month-old female infant exhibited microphthalmia, persistent hyaloidal arteries, and retrolental membranes with total tractional retinal detachments on ultrasound in both eyes. The 22-day-old male newborn exhibited persistent hyaloidal arteries and extensive peripheral avascular retina on angiography in both eyes. Both were found to be positive for the same two pathogenic variants in the RXYLT1/TMEM5 gene, which accounts for approximately 9% of cases of genetically confirmed WWS. CONCLUSION: Siblings with genetically confirmed WWS can have variable presentations despite identical genotype. This highlights the phenotypic disease spectrum of WWS, which may be similar to that seen in familial exudative vitreoretinopathy.

Initial Experience With Biosimilar Bevacizumab-bvzr For Intravitreal Use in Children: A Case Series and Literature Review.

BACKGROUND AND OBJECTIVE: We report our initial experience with intravitreal bevacizumab-bvzr, a bevacizumab biosimilar approved by the US Food and Drug Administration in 2019 and recently introduced by our institution for off-label ophthalmologic use in children. PATIENTS AND METHODS: This was an Institutional Review Board-approved single-institution retrospective case series of pediatric patients 21 years or younger who received at least one intravitreal injection of biosimilar bevacizumab-bvzr. RESULTS: Twelve eyes of 9 patients were identified as having received intravitreal bevacizumab-bvzr, with a total of 13 injections performed. Indications for injection included retinopathy of prematurity (7/13), choroidal neovascularization (3/13), retinal vein occlusion (2/13), and Coats disease (1/13). Following injection of bevacizumab-bvzr, all patients experienced a positive clinical response. No occurrences of postinjection inflammation, intraocular pressure anomalies, or endophthalmitis were observed with a median follow-up of 18 weeks. CONCLUSION: In the absence of controlled studies, this case series supports the use of intravitreal bevacizumab-bvzr as an anti-vascular endothelial growth factor therapy option, including in the pediatric population and resource-poor settings. [Ophthalmic Surg Lasers Imaging Retina 2023;54:84-88.].

Hypertension: A Cause of Bilateral Proliferative Retinopathy.

Purpose: To describe the case of a 67-year-old female with proliferative retinopathy secondary to uncontrolled hypertension. Methods: Retrospective case report including multimodal imaging. Results: A 67-year-old female presented with mild vitreous hemorrhage, retinal hemorrhage, hard exudate of the left eye and hard exudate, copper wiring of vessels, and retinal hemorrhages in the right eye. Optical coherence tomography depicted macular edema of both eyes. Fluorescein angiography revealed large areas of peripheral retinal ischemia and neovascularization with multiple areas of vascular leakage in both eyes. Conclusions: Proliferative hypertensive retinopathy has been rarely reported in the literature. Our patient exhibited findings consistent with proliferative retinopathy secondary to hypertensive retinopathy.

Association of the Pattern of Retinal Capillary Non-Perfusion and Vascular Leakage with Retinal Neovascularization in Proliferative Diabetic Retinopathy.

PURPOSE: To explore the correlation between retinal capillary non-perfusion and the distribution of retinal neovascularization and vascular leakage (VL) in patients with proliferative diabetic retinopathy (PDR). METHODS: Ultra-widefield angiograms of 96 eyes of 69 patients with PDR were reviewed for the proportion of non-perfused area to total gradable area, and for the presence of neovascularization and VL. RESULTS: Retinal neovascularization was distributed as such: neovascularization elsewhere (NVE), 57.3%; neovascularization of the disc (NVD), 11.5%; both neovascularization of the disc and elsewhere (NVED), 31.3%. The proportion of non-perfused retina, so-called ischemic index, was greater in eyes with NVED compared to eyes with NVE only, but not when compared to NVD only. Overall, 83% of eyes had VL. The presence and the extent of VL correlated with the proportion of the ischemic index. While VL and ischemic index were more severe in the mid-periphery and far-periphery, the majority of NVE was located in the posterior pole. CONCLUSIONS: The presence of both NVD and NVE is associated with a greater ischemic index than NVE alone. Although both VL and ischemic index is significantly higher in peripheral zones, the majority of neovascularization occurs at the posterior pole.

Which U.S. States' Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Gender-Affirming Genital Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Services.

BACKGROUND: To date, a comprehensive state-by-state assessment of transgender transition-related health care coverage for gender-affirming hormone therapy (GAHT) and genital gender-affirming surgery (GAS) has not been reported. AIMS: The aims of this study were 1) to verify which U.S. states' Medicaid systems do/do not cover GAHT and GAS; 2) to assess the ease/difficulty for patients to determine whether GAHT and GAS are Medicaid-covered benefits; and 3) to understand possible state-related predictors of Medicaid coverage for gender-affirming care. METHODS: We reviewed the official Medicaid Handbook and website for all 51 states (+D.C.) and 5 territories to confirm whether GAHT and GAS are covered benefits. When indeterminate, we called the Medicaid office in each state, and for many, Medicaid managed care organizations (MCOs), and individual in-state providers, to confirm coverage. We recorded our experiences, number of, and duration of phone calls to confirm coverage. OUTCOMES: The main outcome was a definitive answer from the state/territory's Medicaid program or MCOs regarding whether GAHT and GAS are/are not covered benefits. Secondary outcome measures included responses we received and the total number/duration of phone calls necessary to confirm coverage. RESULTS: Only 12 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAHT in their Medicaid Handbook/webpages. We confirmed that 34 of 51 state Medicaid programs do cover GAHT, whereas 9 of 51 states' and 2 of 5 territories' do not. We could not confirm coverage of GAHT in 8 of 51 states and 3 of 5 territories. Only 26 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAS in their Medicaid Handbook/webpages. We confirmed that 25 of 51 state Medicaid programs do cover GAS, whereas 22 of 51 states' and 3 of 5 territories' do not. We could not confirm coverage of GAS in 4 of 51 states and 2 of 5 territories. Up to 12 calls, lasting up to 125 minutes, were required to confirm coverage for GAHT/GAS. CLINICAL IMPLICATIONS: Our findings indicate that important health care access barriers/disparities exist today and warrant improvement. STRENGTHS & LIMITATIONS: To our knowledge, this is the most comprehensive assessment of transgender transition-related health care coverage. Limitations include possible bias, as it could be that we were more persistent than actual patients would be to determine service coverage, and a lack of specificity regarding which specific hormone formulations or procedures are/are not covered. CONCLUSION: Our findings show that only 34 of 51 (67%) states' Medicaid programs include GAHT and 25 of 51 (49%) include GAS as covered benefits. Our experience suggests that the process to confirm coverage can be especially time-consuming and frustrating for patients. Zaliznyak M, Jung EE, Bresee C, et al. Which U.S. States' Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Genital Gender-Affirming Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Service. J Sex Med 2021;18:410-422.

Writing in the Margins of Sexual Function Questionnaires: A Qualitative Analysis of Data From Women With Pelvic Floor Disorders.

BACKGROUND: The impact of pelvic floor disorders (PFDs) on female sexual function is not well understood, partly due to difficulties in measurement and evaluation. AIM: We sought to assess how women with PFDs respond to sexual function questionnaires through an analysis of survey marginalia, or the comments written in the margins of fixed-choice surveys. METHODS: 94 women with PFDs completed validated written sexual function questionnaires (Global Study of Sexual Attitudes and Behaviors survey, Female Sexual Function Index, and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, International Urogynecological Association-Revised). Marginalia, or the additions, eliminations, and changes subjects made (by hand) to survey items, were collected. Data were coded and analyzed qualitatively using grounded theory methodology. OUTCOMES: Themes and emergent concepts related to the content of survey marginalia were the primary outcomes of this study. RESULTS: We observed 177 instances of marginalia across all questionnaires. Qualitative analysis revealed 7 preliminary themes and 2 emergent concepts. Preliminary themes included partner-related topics, loss, problems during intercourse, emotional problems, other medical problems, and survey answer choices failing to capture the spectrum of patient experiences. Emergent concepts revealed highly diverse sexual function in this population and a wide range of factors that influence sexual function. CLINICAL IMPLICATIONS: Conducting qualitative studies alongside sexual function questionnaires can allow for a more meaningful assessment of the sexual function of women with various underlying conditions, such as PFDs. STRENGTHS & LIMITATIONS: This is the first study of its kind to analyze survey marginalia from sexual function questionnaires among women with PFDs. The limitations of this study include the inherently spontaneous nature of marginalia data. In addition, the ways in which study participants responded to sexual function questionnaires in our study may not be reflective of all potential subjects. CONCLUSION: Analysis of survey marginalia from sexual function questionnaires amongst women with PFDs revealed new information regarding patients' histories, concerns, and thoughts. Over half of the women in this study felt the need to expand, explain, or eliminate responses from the questionnaires. Many subjects were no longer sexually active, which accounted for a large majority of participants leaving questions blank or responding with "N/A." Standard sexual evaluation tools may fail to capture the complexity, spectrum, and depth and breadth of patient experiences. Parameshwar PS, Borok J, Jung E, et al. Writing in the Margins of Sexual Function Questionnaires: A Qualitative Analysis of Data From Women With Pelvic Floor Disorders. J Sex Med 2020;17:1705-1714.

Vision loss, gaze palsy, and nystagmus in a patient with leukemia.

A 22-year old male with a history of B-cell acute lymphoblastic leukemia with recent bone marrow transplantation and on immunosuppressive therapy presented with painless, subacute vision loss of two weeks duration. He exhibited a horizontal gaze palsy, nystagmus, and mildly swollen and hyperemic optic discs with peripapillary flame hemorrhage on retinal exam. He had bilateral cecocentral scotomas on visual field exam, and MRI of his brain/orbits demonstrated hyperintensities in the hypothalamus, periaqueductal gray, and dorsal rostral medullary regions. After continued progression of symptoms despite discontinuation of the patient's tacrolimus, an empiric trial of IV thiamine treatment was started before the patient's lab vitamin levels were available, given strong clinical suspicion for a nutritional etiology. The patient's clinical presentation improved dramatically, and he achieved a final visual acuity of 20/20, full visual fields bilaterally, and resolution of nystagmus. A final diagnosis of Wernicke's encephalopathy was supported by his clinical course, imaging findings, and further confirmation with blood thiamine levels. This case presents unique ocular manifestations of Wernicke's encephalopathy and highlights the importance of early diagnosis in this potentially reversible condition.

Synchronous recurrence of concurrent colon adenocarcinoma and dedifferentiated liposarcoma.

A 62-year-old man presented with concurrent sigmoid colon adenocarcinoma and small bowel mesenteric dedifferentiated liposarcoma. Following surgical resection of the colon cancer, complete excision of the mesenteric sarcoma and adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy, the patient demonstrated no radiological evidence of disease for more than 2 years. The patient then developed synchronous recurrence of both cancers: the colon cancer metastasised to the liver and a pelvic lymph node, and the liposarcoma recurred in the original location. The patient underwent additional chemotherapy with complete response of the metastatic colon cancer and stable disease for the liposarcoma. The recurrent mesenteric tumour was subsequently resected. Although concurrent cancers have been reported, this unique case of synchronous recurrence raises interesting hypotheses regarding host-tumour interaction and immune surveillance.

The role of parathyroidectomy in JAK2 mutation negative polycythemia vera.

The relationship between polycythemia vera (PV) and primary hyperparathyroidism is not well understood. Remission or improvement of PV following parathyroidectomy in the setting of primary hyperparathyroidism has previously been described; however, long-term outcomes are not well characterized. We describe a patient with JAK2 mutation negative PV and primary hyperparathyroidism, with a dramatic, but ultimately transient, improvement in hemoglobin following resection of a parathyroid adenoma. While screening for hyperparathyroidism may be useful in the setting of PV, indications for parathyroidectomy should be driven by symptomatology or established criteria, not the desire to affect the clinical course of PV.