Multimodal Retinal Imaging Findings in Hardikar Syndrome.

PURPOSE: To describe the syndromic, clinical, and retinal findings of a patient with an extremely-rare genetic condition known as Hardikar Syndrome (HS) with presentation of optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiographic (FA), and indocyanine green angiographic (ICG) findings. METHODS: Clinical course was detailed and followed over time with examinations and multimodal imaging. PATIENT AND RESULTS: A 17-year-old patient with HS was referred for possible retinitis pigmentosa. Dilated fundoscopic examination revealed large, multifocal cauliform patches of chorioretinal retinal pigment epithelium (RPE) changes with RPE drop-out involving the macula and periphery in both eyes. Additionally, an inactive choroidal neovascular membrane (CNVM) was present in the left eye. Multimodal imaging with OCT, FAF, FA and ICG correlated with the clinical findings of focal patches of chorioretinal degeneration in both eyes. Additionally, an anomalous finding of the superior retinal arterial vessels filling in tandem with the choroidal was present in the left eye. The patient's clinical findings were consistent with HS, and genetic testing with whole exome sequencing revealed a pathogenic mutation in the MED12 gene, confirming diagnosis. DISCUSSION AND CONCLUSIONS: HS is associated with RPE degeneration, creating focal patches of pigmentary chorioretinal atrophic lesions. Vision loss can occur due to the development of CNVMs. We recommend close evaluation and follow-up for HS patients with multimodal retinal imaging.

Vitreoretinopathy-Associated Pediatric Retinal Detachment Treatment Outcomes: IRIS® Registry (Intelligent Research in Sight) Analysis.

Purpose: To determine the treatment patterns and outcomes of pediatric retinal detachments (RDs) associated with hereditary vitreoretinopathies. Design: Retrospective cohort analysis using IRIS® Registry (Intelligent Research in Sight) database. Participants: Patients < 18 years old with a rhegmatogenous RD and a systemic disorder associated with vitreoretinal degeneration (e.g., Stickler syndrome) or other malformation of the vitreous from 2013-2019. Methods: Cases were identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9, ICD-10) diagnostic codes from the IRIS® Registry cohort. Other hereditary vitreoretinopathies that are not encoded by specific ICD code(s) were captured by text search. Nonspecific vitreous abnormality ICD codes were also included. Exclusion criteria included traumatic retinal detachments using ICD codes for ocular trauma and serous or exudative retinal detachment. Surgical procedures were identified using Current Procedural Terminology (CPT) codes for repair of retinal detachment. Baseline demographic information collected included age, gender, race/ethnicity, geographic region of the provider location, and health insurance status. Main Outcome Measures: Main outcomes measured in this study were average time to first surgery, number of eyes presenting with bilateral detachments, and choice of initial surgical procedure. Results: A total of 2115 eyes of 1722 patients were identified (mean age, 10.4 years; 58% male). The median time to first surgery was 7 days (interquartile range, 40 days). One thousand four hundred seven eyes of 1134 patients had ≥ 1 year of follow-up, with 506 eyes (36%) developing a fellow eye RD. Thirty-three percent of patients presenting with bilateral detachments, and 349 eyes had initial RD surgery within 1 year of the index date documented by CPT code. Fellow eye detachment occurred a mean of 32 days after initial presentation. The mean number of surgeries per eye within 1 year was 1.68. Best-corrected visual acuity did not improve from a baseline 20/54 to 20/62. The initial procedure was most commonly complex RD repair (n = 176), followed by scleral buckle (n = 102), pars plana vitrectomy (n = 89), laser (n = 59), cryotherapy (n = 5), and pneumatic retinopexy (n = 5). There were 51 new diagnoses of glaucoma and 37 new diagnoses of aphakia within 1 year after the surgical procedure. Conclusions: IRIS Registry data provide insight into rare pediatric vitreoretinopathy-associated RDs, which have a high rate of reoperation and fellow eye involvement. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Retinal Detachment Prophylaxis for Patients With Stickler Syndrome: A Survey of Pediatric Retinal Specialist Treatment Preferences.

BACKGROUND AND OBJECTIVE: Stickler syndrome is the most common inherited cause of pediatric rhegmatogenous retinal detachment. The purpose of this study was to survey pediatric retinal surgeon preferences for prophylactic treatment of Stickler syndrome patients. STUDY DESIGN: A voluntary, anonymous 27-question survey was developed by RedCap and distributed to the Association of Pediatric Retinal Surgeons. The survey was distributed on March 17, 2021. Results were tabulated on April 12, 2021 in Microsoft Excel. All surveys returned were included. RESULTS: Thirty-four (76% response rate) respondents completed the survey. Twenty-six (76%) reported primarily using prophylactic laser retinopexy, four (12%) preferred use of cryotherapy, and 12% reported using prophylactic scleral buckle. CONCLUSIONS: The majority of the United States. and international pediatric retinal surgeons use laser retinopexy as the primary method of prophylactic treatment. These results may serve as a benchmark for retinal surgeons less familiar with prophylactic treatment approaches. [Ophthalmic Surg Lasers Imaging Retina 2023;54:102-107.].

Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab.

PURPOSE: The purpose of this study is to review the neonatal and early childhood course of children who were treated with intravitreal bevacizumab for APROP and identify any long term limitations these children face years after treatment. METHODS: This retrospective consecutive case series reviewed both ophthalmologic and pediatric medical records to determine ocular and neurologic function following treatment with a single injection of intravitreal bevacizumab (IVB) for APROP. Patient records were reviewed to identify the gestational age, average birth weight, gender, post-menstrual age (PMA) at the time of injection, regression status, rescue therapy events, final visual acuity, final refraction, ophthalmologic diagnoses and complications, neurologic diagnoses, and duration of follow up. RESULTS: The study included 43 eyes from 13 male and 9 female children. The average gestational age was 24 weeks and average birth weight was 625.2 grams. The average follow-up was 4.08 years (range: 1.85-7.36 years). The average PMA at time of bevacizumab injection was 35.59 weeks. Thirty-five eyes eventually received laser photocoagulation at an average PMA of 53.17 weeks. All eyes in this study demonstrated regression without progression to retinal detachment. At last follow up, 67% (29/43) of eyes were able to discern letters or shapes, with an average visual acuity of 20/37. 16 (72%) children were diagnosed with perinatal neurological disorders. 59% (n = 13) developed chronic neurological impairment, 77% (n = 10) of whom developed neurodevelopmental delay. Several infants were diagnosed with endocrine disease or genetic syndromes. CONCLUSIONS: Extreme prematurity is associated with significant morbidity. Nearly all infants (92%) who developed chronic neurologic disease were diagnosed with neurologic disease during the perinatal period. Intravitreal bevacizumab, often with adjuvant photocoagulation, led to regression without detachment in 100% of eyes, with most verbal children retaining functional vision.

Risk and Prevention of Retinal Detachments in Patients with Stickler Syndrome.

BACKGROUND AND OBJECTIVE: To report the impact of prophylactic laser retinopexy in the prevention of retinal detachments (RDs) in patients with Stickler syndrome. PATIENTS AND METHODS: This was a retrospective, comparative case series of patients with Stickler syndrome from the year 2000 to 2019. We compared the rate of RDs between individuals who did and did not receive prophylactic laser therapy. In patients with an RD, we compared the rate of RD in the fellow eye with and without prophylactic laser treatment. RESULTS: A total of 95 eyes were identified. Fifty-four percent of the overall population was female. The RD rate was 26.7% among eyes without previous prophylactic laser retinopexy and 4.6% among eyes with previous prophylactic laser retinopexy. A Cox proportional model revealed that laser prophylaxis treatment had a statistically significant effect on the risk of RD or retinal tear during the 25-year survival period from birth (P = .034). Eyes receiving treatment were 70% less likely to experience RD or retinal tear (hazard ratio, 0.297; 95% CI, 0.097 to 0.913). CONCLUSIONS: This study's results suggest a potential role for prophylactic laser retinopexy in the prevention of rhegmatogenous RD among patients with a clinical diagnosis of Stickler syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:7-11.].

Acute anterior uveitis after topical interferon for conjunctival intraepithelial neoplasia (CIN).

Objective: Ocular surface squamous neoplasia (OSSN) is the most common type of non-melanocytic ocular surface tumor. Conjunctival intraepithelial neoplasia (CIN) is a type of OSSN that be medically managed by either topical interferon alpha-2b (IFN α-2b), 5-fluorouracil (5-FU), or mitomycin C. While a paradoxical response to IFN α-2b in the HIV population has been reported, we report a case of a paradoxical response in an immunocompetent individual. Methods: A 65-year-old immunocompetent female presents to the clinic with CIN. Results: She is started on topical IFN α-2b, resulting in an unexpected hypopyon, increased corneal epithelial defect, and increased size of the lesion. Switching to topical 5-FU resulted in decreasing size of the CIN lesion and resolution of the epithelial defect. Conclusions: Topical IFN α-2b can produce a paradoxical worsening of CIN lesions in some patients. Providers should be aware of this reaction, as well as the presenting signs and symptoms, to make appropriate treatment changes when treating CIN.

Short term visual and structural outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment delay during the first COVID-19 wave: A pilot study.

Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The 'COVID-19 lockdown' was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.

Bilateral Ocular Ischemic Syndrome in the Setting of Chronic Angle Closure Glaucoma.

We report novel case of a 57-year-old woman who developed bilateral ocular ischemic syndrome in the setting of chronic angle closure glaucoma without associated angle neovascularization. Detailed is a course in which markedly prolonged, elevated intraocular pressure led to significantly reduced arterial perfusion at the level of the central retinal artery, leading to the clinical picture of ocular ischemic syndrome.

Inpatient Adherence to Topical Glaucoma Medications before and after an Educational Intervention.

PURPOSE: To assess the inpatient adherence rate and factors associated with adherence to topical glaucoma medications (TGMs) at a single academic institution throughout hospitalization before and after an educational intervention. DESIGN: Nonrandomized, comparative, retrospective study. PARTICIPANTS: Inpatients 18 years of age and older admitted to a single academic hospital from January 2014 through June 2019 with a diagnosis of glaucoma who also received TGMs. METHODS: The medication administration record during admission was examined closely to determine if the TGMs were reconciled and administered correctly before and after an educational intervention with inpatient providers. A simple intervention reached various health care providers through an educational e-mail, communication in a weekly newsletter, and a morning report presentation. Adherence was defined as administration of more than 75% of recommended doses during the inpatient stay. Other collected variables included length of stay and primary diagnosis on admission. MAIN OUTCOME MEASURES: Adherence rate to inpatient administration of TGMs. RESULTS: One hundred eighty-four patients (n = 142 before intervention; n = 42 after intervention) were included. The preintervention group had a total of 275 TGMs, of which 207 (75.3%) were administered in accordance with the adherence definition of this study. After the intervention phase, 49 of 56 (87.5%) TGMs were administered with appropriate adherence (P = 0.047). Adherence was associated significantly with a known outpatient medication regimen (P = 0.006) and correct admission reconciliation (P < 0.001). CONCLUSIONS: When glaucoma patients requiring topical treatment are admitted, approximately one quarter of patients seem to not receive their medications appropriately. In this study, a simple educational intervention was able to improve adherence. To prevent daily fluctuations in intraocular pressure for vulnerable glaucoma patients, inpatient adherence to appropriate medication administration should be stressed continuously. While in the care of health care providers, inpatients should be afforded at least the opportunity to maintain adequate adherence, just as is carried out for other medications related to other chronic medical conditions.

Adams-Oliver syndrome: a case of bilateral progressive ischemic maculopathy.

Adams-Oliver syndrome (AOS) is a congenital condition characterized by aplasia cutis congenita of the scalp and transverse limb defects. Other clinical features reported in association with AOS include cardiac malformations, cutis marmorata telangiectatica congenita, prenatal complications, and ophthalmic abnormalities. Reported ophthalmic manifestations range from Peters anomaly-like findings and cataract formation to incomplete or abnormal retinal vasculature, optic nerve hypoplasia, and rod dystrophy. We report the novel case of a 3-month-old boy with AOS type 2 who was found to have bilateral progressive macular ischemia.

Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk.

Although numerous genetic loci have been associated with coronary artery disease (CAD) with genome wide association studies, efforts are needed to identify the causal genes in these loci and link them into fundamental signaling pathways. Recent studies have investigated the disease mechanism of CAD associated gene SMAD3, a central transcription factor (TF) in the TGFß pathway, investigating its role in smooth muscle biology. In vitro studies in human coronary artery smooth muscle cells (HCASMC) revealed that SMAD3 modulates cellular phenotype, promoting expression of differentiation marker genes while inhibiting proliferation. RNA sequencing and chromatin immunoprecipitation sequencing studies in HCASMC identified downstream genes that reside in pathways which mediate vascular development and atherosclerosis processes in this cell type. HCASMC phenotype, and gene expression patterns promoted by SMAD3 were noted to have opposing direction of effect compared to another CAD associated TF, TCF21. At sites of SMAD3 and TCF21 colocalization on DNA, SMAD3 binding was inversely correlated with TCF21 binding, due in part to TCF21 locally blocking chromatin accessibility at the SMAD3 binding site. Further, TCF21 was able to directly inhibit SMAD3 activation of gene expression in transfection reporter gene studies. In contrast to TCF21 which is protective toward CAD, SMAD3 expression in HCASMC was shown to be directly correlated with disease risk. We propose that the pro-differentiation action of SMAD3 inhibits dedifferentiation that is required for HCASMC to expand and stabilize disease plaque as they respond to vascular stresses, counteracting the protective dedifferentiating activity of TCF21 and promoting disease risk.