INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.

GENDER DIFFERENCES IN SELF-REPORTED PROCEDURAL VOLUME AMONG VITREORETINAL FELLOWS.

PURPOSE: A prior study revealed discrepancies in self-reported surgical numbers between male and female ophthalmology residents. This study further investigates the gender differences in self-reported procedural volume among vitreoretinal surgery fellows and examines the differences for surgical, medical, and total self-reported procedural volume between male and female vitreoretinal fellows. METHODS: A retrospective review of case logs submitted to the American Society of Retina Specialists by first-year and second-year vitreoretinal fellows from July 1, 2018, to June 30, 2019, was performed. Fellows who reported fewer than 100 pars plana vitrectomies were excluded. A total of 133 fellows were included. RESULTS: Overall, 37 of 57 (65%) first-year fellows and 59 of 76 (78%) second-year fellows were male. An average of 1,120 procedures were self-reported among all vitreoretinal fellows. In the group of second-year fellows at the completion of fellowship, men reported more total procedures (1,171 [864-1,600] vs. 1,005 [719-1,257]; P = 0.072). Women reported statistically significant fewer endolaser (P = 0.018), internal limiting membrane peel (P = 0.042), and cryoretinopexy (P = 0.002) procedures compared with men. When splitting the data by total surgical versus medical procedures, men reported more procedures than women both surgically (1,077 [799-1,490] vs. 925 [622-1,208]; P = 0.085) and medically (72 [41-116] vs. 56 [20-94]; P = 0.141), although these differences were not statistically significant. CONCLUSION: There is a trend for female vitreoretinal fellows to report fewer surgical procedures than their male counterparts, raising concerns for gender gaps in vitreoretinal surgical training. Further research is needed to verify this discrepancy and identify potential barriers that female vitreoretinal surgeons are facing in training.

Zygomatic dental implant induced orbital fracture and inferior oblique trauma.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.

Alström syndrome: Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center.

Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m2 and proteinuria); all were adults with median age of 32.8 (20.6-37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.

Clinical and Optical Coherence Tomography Comparison Between Ocular Surface Squamous Neoplasia and Squamous Metaplasia.

PURPOSE: The purpose of this study was to compare the clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal squamous metaplasia and ocular surface squamous neoplasia (OSSN). METHODS: A retrospective case-control study of 8 patients, 4 with histologically confirmed squamous metaplasia and 4 with histologically confirmed OSSN, who presented to the Miami Veterans Administration Medical Center and Bascom Palmer Eye Institute between 2016 and 2020 was performed. Clinical characteristics, HR-OCT findings, and pathology were evaluated and compared. RESULTS: Four patients with squamous metaplasia and 4 with OSSN were evaluated. In the metaplasia group, 75% were male, 2 were White, and 2 were Black. In the OSSN group, all 4 were White males. All lesions were opalescent and occurred at the limbus; however, the borders were more smooth and rounded in the metaplastic lesions compared with OSSN. HR-OCT findings were indistinguishable between the 2 groups. CONCLUSIONS: There is overlap in clinical characteristics and HR-OCT findings between corneal squamous metaplasia and OSSN, highlighting one limitation of HR-OCT. As such, if a corneal opacity has some but not all HR-OCT findings of OSSN, squamous metaplasia should also be considered. A biopsy may be indicated to further evaluate and guide treatment.

Acute abducens nerve palsy following COVID-19 vaccination.

We report the case of a healthy 59-year-old woman who presented with an acute abducens nerve palsy 2 days after receiving the Pfizer-BioNTech COVID-19 vaccine. In adults, such palsies are typically caused by microvascular disease or compressive tumors, although they have also been described after routine vaccinations. Given the temporal relationship between vaccination and the onset of symptoms, the lack of preexisting medical conditions, and unremarkable magnetic resonance imaging, the patient's abducens nerve palsy was felt to be related to her vaccination. This case highlights the importance of recognizing the potential of a COVID-19 vaccine to have neurologic sequelae similar to those that as have been reported with the virus itself as well as with other vaccines.

Trends in Endophthalmitis Associated With Intravitreal Injection of Anti-VEGF Agentsat a Tertiary Referral Center.

BACKGROUND AND OBJECTIVE: To report the incidence and clinical features of infectious endophthalmitis after intravitreal (IV) injection of anti-vascular endothelial growth factor inhibitors (VEGF) between 2018 and 2020 and to compare to prior rates. PATIENTS AND METHODS: Retrospective analysis of patients with endophthalmitis after anti-VEGF IV injections treated at Bascom Palmer Eye Institute between January 1, 2018, and December 31, 2020. RESULTS: Between 2018 and 2020, the rate of clinically diagnosed endophthalmitis was 0.014% (10/71,858) and of culture-positive was 0.008% (6/71,858). Clinically diagnosed endophthalmitis rates per injection were: aflibercept (0.022%); ranibizumab (0.019%); bevacizumab (0%); and brolucizumab (0%). Clinically diagnosed endophthalmitis rates were similar in the present study compared to those from 2005 to 2017 (P = .84). Fifteen eyes were diagnosed with endophthalmitis (10 in-house, five external referrals). Of culture-positive eyes, the organisms were coagulase-negative Staphylococcus (8/11), Streptococcus species (2/11), and Abiotrophia defectiva (1/11). A universal face-masking policy in 2020 did not lower infection rates (P = .73). CONCLUSION: Endophthalmitis rates after IV anti-VEGF remain low and are similar to prior reports. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:319-326.].

Nutritionally variant streptococci causing endophthalmitis associated with intravitreal anti-vascular endothelial growth factor injection.

PURPOSE: To describe the clinical course and microbial properties of the first two reported cases of nutritionally variant Streptococci (Granulicatella adiacens and Abiotrophia defectiva) endophthalmitis following intravitreal anti-vascular endothelial growth factor injection (IVI). OBSERVATIONS: A 74 year-old female developed Granulicatella adiacens endophthalmitis following IVI. The patient underwent a pars plana vitrectomy and visual acuity recovered to 20/30 in six weeks. Similarly, an 88 year-old male developed Abiotrophia defectiva endophthalmitis after IVI. After a pars plana vitrectomy, the visual acuity recovered to 20/60 at five weeks. CONCLUSIONS AND IMPORTANCE: Endophthalmitis due to Streptococcus species has traditionally resulted in uniformly poor visual outcomes. However, nutritionally variant Streptococci, now reclassified as Granulicatella and Abiotrophia species, appear to have a less aggressive clinical course and better visual acuity outcomes. To the authors' knowledge, these are the first reports of nutritionally variant Streptococci following IVI related endophthalmitis.

Agrobacterium radiobacter Endophthalmitis Associated with Baerveldt Tube Exposure.

Agrobacterium radiobacter is a Gram-negative bacillus and a rare cause of endophthalmitis. An 85-year-male presented with late-onset endophthalmitis associated with exposure of an inferonasal Baerveldt tube. The patient was initially treated with anterior chamber paracentesis and intravitreal antibiotics. Aqueous humor culture revealed A. radiobacter resistant to cefazolin, ceftazidime, amikacin, tobramycin, and trimethoprim-sulfamethoxazole. Subsequently, the patient underwent explantation of the glaucoma drainage implant (GDI). After initial improvement, the patient had clinical worsening and was diagnosed with recurrence. Subsequent treatment involved explantation of the second GDI in addition to pars plana vitrectomy with silicone oil infusion, intraocular lens removal, and administration of intravitreal antibiotics. Visual acuity improved but remained at count fingers at 2 weeks. This is the first reported patient with A. radiobacter endophthalmitis associated with an exposed GDI. This report illustrates the resistant nature of this organism in addition to the efficacy of silicone oil administration and intraocular prosthesis explantation.

Postoperative Correction and Drift After Vertical Rectus Muscle Transposition for Total Sixth Cranial Nerve Palsy.

PURPOSE: To determine the magnitude of change between the preoperative and postoperative alignment and amount of postoperative drift for two vertical rectus muscle transpositions (VRTs). METHODS: Retrospective review of medical records of patients with total sixth cranial nerve palsy who underwent VRT procedures. The primary outcome measure was the magnitude of esotropia in prism diopters (PD) at the preoperative and postoperative visits. RESULTS: Twenty-seven patients were included. Sixteen had full tendon transposition with Foster augmentation (FTT+FA) and 11 had partial tendon transposition with resection and simultaneous medial rectus recession (PTT+R+MRR). A larger correction was obtained with PTT+R+MRR (mean ± standard deviation [SD]: 52 ± 19 PD; range: 27 to 87 PD) when compared to FTT+FA (mean: 40 ± 13 PD; range: 15 to 68 PD). At postoperative month 2, a greater esotropic drift was noted in the PTT+R+MRR group (16 PD) than the FTT+FA group (6 PD). Although the difference in the amount of correction was not statistically significant (P = .071), the difference in the amount of drift was statistically significant (P = .009). CONCLUSIONS: There was a trend toward greater correction with PTT+R+MRR than FTT+ FA, but it was not statistically significant. FTT+FA had significantly less postoperative drift than PTT+R+MRR. The results suggest that a small immediate postoperative overcorrection may be desirable in some VRT procedures. [J Pediatr Ophthalmol Strabismus. 2019;56(4):238-242.].

Association between congenital nasolacrimal duct obstruction and mode of delivery at birth.

PURPOSE: To investigate the association between mode of delivery, incidence of congenital nasolacrimal duct obstruction (CNLDO), and treatment outcomes. METHODS: The medical records of children diagnosed with CNLDO at a tertiary referral center between 2012 and 2017 were analyzed retrospectively. Patient demographics, pregnancy and birth history, clinical characteristics of CNLDO, and treatment outcomes were compared in patients delivered via Cesarean section (CS) versus vaginal delivery (VD). The rates of CS, as well as full-term and premature births, were also compared to Miami-Dade County normative values to eliminate the confounding effects of prematurity. RESULTS: A total of 104 patients were included. A significantly higher percentage of patients with CNLDO (61%) were delivered via CS (P < 0.0001). Among full-term babies, there was 55% greater risk (OR = 1.55; 95% CI, 0.98-2.43; P = 0.067) of CNLDO for CS birth compared to all other babies. Among preterm babies, there were no significantly greater odds of CNLDO for CS compared to VD births (P = 0.575). CNLDO did not resolve spontaneously in 50 patients, including 37 CS (74%) and 13 VD (26%) patients (P = 0.007). Among those patients who failed first-line probing, 86.2% were born via CS, whereas 13.8% were born via VD (P = 0.0009). CONCLUSIONS: CS is a risk factor for CNLDO, independent of gestational age. Children born via CS also tend to have a more complicated clinical course requiring additional surgical interventions.

Aggressive Posterior Retinopathy of Prematurity and a TUBA1A Mutation inde Morsier Syndrome.

The authors report a case of a premature male neonate born at 25.3 weeks gestational age weighing 605 grams with septo-optic dysplasia (SOD) and a heterozygous mutation in TUBA1A c.715A>C, a critical gene for microtubules, who developed asymmetric and aggressive posterior retinopathy of prematurity (ROP). This report presents a novel mutation associated with SOD and proposes that optic nerve hypoplasia may have potentiated a severe ROP phenotype. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:629-632.].

Comprehensive Endocrine-Metabolic Evaluation of Patients With Alström Syndrome Compared With BMI-Matched Controls.

Background: Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements. Objective: We sought to characterize the endocrine and metabolic features of AS while accounting for obesity as a confounder by comparing patients with AS to body mass index (BMI)-matched controls. Methods: We evaluated 38 patients with AS (age 2 to 38 years) who were matched with 76 controls (age 2 to 48 years) by age, sex, race, and BMI. Fasting biochemistries, mixed meal test (MMT), indirect calorimetry, dual-energy X-ray absorptiometry, and MRI/magnetic resonance spectroscopy were performed. Results: Frequent abnormalities in AS included 76% obesity, 37% type 2 diabetes mellitus (T2DM), 29% hypothyroidism (one-third central, two-thirds primary), 3% central adrenal insufficiency, 57% adult hypogonadism (one-third central, two-thirds primary), and 25% female hyperandrogenism. Patients with AS and controls had similar BMI z scores, body fat, waist circumference, abdominal visceral fat, muscle fat, resting energy expenditure (adjusted for lean mass), free fatty acids, glucagon, prolactin, ACTH, and cortisol. Compared with controls, patients with AS were shorter and had lower IGF-1 concentrations (Ps ≤ 0.001). Patients with AS had significantly greater fasting and MMT insulin resistance indices, higher MMT glucose, insulin, and C-peptide values, higher HbA1c, and higher prevalence of T2DM (Ps < 0.001). Patients with AS had significantly higher triglycerides, lower high-density lipoprotein cholesterol, and a 10-fold greater prevalence of metabolic syndrome (Ps < 0.001). Patients with AS demonstrated significantly greater liver triglyceride accumulation and higher transaminases (P < 0.001). Conclusion: Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development.

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader-Willi syndrome.

OBJECTIVE: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects. METHODS: We studied eCB 'tone' in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice. RESULTS: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB 'tone', manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days) reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype. CONCLUSIONS: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS.