Ocular Exam Research Articles

An Unknown Pregnancy Presenting as Vision Loss: A case report

Hypertensive retinopathy (HTR) secondary to preeclampsia can present similarly to non-pregnancy related HTR. Here, we report a case of a patient who presented to our eye clinic for decreased vision bilaterally. Ocular exam and imaging revealed large serous retinal detachments affecting the central macula along with massive intraretinal edema. Due to concern for systemic pathology, the patient was referred to the emergency department (ED), where her blood pressure was found to be 200/110 mmHg. The patient was discovered to be pregnant and diagnosed with preeclampsia with severe features in the third trimester. After delivery of the fetus, the patient had complete resolution of visual symptoms. Since pregnancy-related ophthalmic manifestations are generally mild and reversible, ophthalmologists do not usually consider pregnancy-related disease in patients who are not known to be pregnant. However, it is important to keep these complications on the differential with women of child-bearing age.

Discriminating Diseases Mimicking Normal-Tension Glaucoma (NTG) from NTG.

Background/Objectives: The aim of this study was to identify the most reliable ocular exam and establish a threshold for deciding whether to perform neuroimaging in order to screen for diverse diseases other than normal-tension glaucoma (NTG). A retrospective, observational, comparative study was used. Methods: In total, 106 individuals with atypical features of NTG who underwent glaucoma assessments and contrast-enhanced MRI of the brain or orbit were included. The criteria for atypical NTG included the following: (1) unilateral normal-tension glaucoma, (2) visual field (VF) damage inconsistent with optic disc appearance, (3) fast VF progression, (4) worsening of visual acuity, (5) optic disc pallor, (6) scotoma restricted by a vertical line, and (7) central scotoma. Glaucoma evaluations included measurements of visual acuity, intraocular pressure, central corneal thickness, axial length, cup-disc ratio, retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, mean deviation (MD), and visual field index (VFI). Statistical analyses involved independent t-tests, receiver operating characteristic (ROC) curves, and area under the curve (AUC) in order to differentiate neuro-ophthalmological conditions from NTG, compare the diagnostic power of each factor, and determine the cut-off value. Results: Relatively fewer diagnoses of non-glaucomatous diseases were associated with unilateral NTG, the worsening of VA, and central scotoma. Factors such as rapid visual field progression, optic disc pallor, and scotoma restricted by a vertical line had a relatively higher diagnostic rate of non-glaucomatous diseases. There were significant differences in average RNFL and GCIPL thicknesses at the nasal quadrant between NTG and NTG-mimicking conditions. Only the GCIPL thickness at the nasal quadrant had reliable power for discriminating between neuro-ophthalmological disease and NTG. For the GCIPL thickness at the nasal quadrant, the AUC was 0.659, and the cut-off value was 65.75. Conclusions: When deciding whether to proceed with imaging, such as carrying out an MRI test, for NTG patients with atypical NTG characteristics, it would be advisable to consider the nasal sector cut-off value of GCIPL thickness.

Ophthalmological Examination and Imaging Features that Better Predict Risk of Angle Closure in Siblings

Characteristics of individuals with angle closure may be useful in targeted screening of family members. Here, we assess if findings gathered during examination and imaging of patients with a known angle closure diagnosis (probands) could better determine the risk of angle closure in the patients' siblings. Cross-sectional study of patients with known angle closure and their siblings. Participants, and Controls: South Indian patients (probands) 30 years and older with open angles, suspect primary angle closure (PACS), or primary angle closure/primary angle closure glaucoma (PAC/PACG), and a biological sibling age 30 years or older (n=292 proband/sibling pairs). Demographic data, relevant ocular history, and a comprehensive ophthalmic examination with Anterior Segment Optical Coherence Tomography (ASOCT) were obtained. Three clinically relevant models were created to analyze the contribution of specific proband factors in predicting sibling angle closure diagnosis, using demographic (age, gender), ocular exam (gonioscopy, optic nerve exam, visual acuity, intraocular pressure [IOP]), and ASOCT features to improve prediction beyond proband diagnosis alone evaluated by log likelihood ratio testing and statistical comparison of receiver operating characteristics (ROC). Sibling angle closure diagnostic accuracy. Demographic and ocular exam metrics did not improve the prediction of sibling angle closure for all three outcomes (sibling diagnosis: (1) PACS/PAC/PACG vs OA, (2) PAC/PACG vs PACS/OA, and (3) PAC/PACG vs PACS), adding no model improvement when compared to diagnosis alone. Models adding ASOCT metrics to the prior model including proband diagnosis, demographics and ocular exam measures led to significantly improved prediction of 2 of the 3 angle closure outcomes. Specifically, improvement was noted via likelihood ratio testing for prediction of PAC/PACG vs PACS/OA (p=0.01), or PAC/PACG vs PACS (p=0.001). For all 3 angle closure outcomes, ROC comparisons demonstrated significant improvement in AUC between the three models predicting sibling outcomes, demonstrating an increase in AUC with each successive nested model across all 3 sibling angle closure outcomes. Structural features of eyes with angle closure may assist in stratifying the risk of angle closure in patients' siblings. Further studies should consider evaluating this approach to achieve more targeted screenings.

Adalimumab in the Treatment of Complex Sarcoidosis-related Inflammatory Eye Disease: A Case Series

Background: Sarcoidosis is a systemic granulomatous inflammatory disease that is associated with inflammatory eye manifestations such as uveitis, cystoid macular edema, and retinal vasculitis. Although Corticosteroids (CS) have traditionally been the mainstay of treatment, there is a clinical need and growing interest in exploring alternative therapeutic options for patients who are refractory to or intolerant of CS or require long-term steroid-sparing agents. Purpose: This case series aims to describe the effectiveness of adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, in the management of complex sarcoidosis-related inflammatory eye disease via reduction in CS dosage and ocular exam findings before and after initiation of adalimumab therapy. Method: A retrospective chart review of patients between 2010 and 2023 seen at our academic center’s rheumatology and eye clinics was conducted, with 5 patients meeting the inclusion criteria. Results: Most patients were able to lower, discontinue, or remain off oral CS, while all 5 patients demonstrated a reduction in uveitis activity, Cystoid Macular Edema (CME), and/or retinal vasculitis. Conclusion: These findings suggest a potential role for adalimumab as an effective and safe therapeutic option in the management of complex sarcoidosis-related inflammatory eye disease.

Prognostic indicators of corneal ulcer clinical outcomes at a tertiary care center in the Bronx, New York

PurposeCorneal ulcers frequently result in ocular morbidity and may lead to permanent visual impairment if severe or untreated. This study aims to evaluate the association of patient factors and ocular exam findings on clinical outcomes for patients diagnosed with a corneal ulcer at a tertiary care center in the Bronx, New York.MethodsA retrospective chart review was conducted on all ambulatory and admitted patients diagnosed with a corneal ulcer (identified using ICD-10 code H16.0) at Montefiore Medical Center, Bronx, NY between 2016–2022. Patient demographics, presence of known risk factors, characteristics of subsequent clinical course, and microbiological studies were noted. Clinical outcomes following treatment were longitudinally evaluated and categorized based upon the following criteria: 1) ‘No Surgical Intervention’: No severe complications or surgery required after presentation, 2) ‘Surgical Intervention’: Decline in BCVA with surgery required for a severe complication.ResultsThe search criteria identified 205 patients (205 eyes) with the diagnosis of a corneal ulcer. Mean age was 55.3 ± 21.1 years (mean ± SD). Mean ulcer area at presentation was 7 ± 10.5 mm2. Mean LogMAR at presentation was 1.2 ± 1, and following treatment, improved to 1.0 ± 1. ‘Surgical Intervention’ outcome was associated with advanced age (p = 0.005), presence of ocular surface disease (p = 0.008), central location of ulcer (p = 0.014), greater ulcer area at presentation (p = 0.003), worse visual acuity at presentation (p < 0.001), and isolation of fungi (p = 0.004).ConclusionIdentification of risk factors associated with a poor clinical prognosis can guide treatment and inform expectations for patients diagnosed with a corneal ulcer. Our study highlights the importance of timely diagnosis, work-up, and initiation of appropriate management, particularly in vulnerable populations where access to specialty care is logistically challenging.

Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE. Methods: A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap. Results: This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study's start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity. Conclusion: Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE.

CLINICAL AND HISTOPATHOLOGIC OCULAR FINDINGS IN AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS).

Cownose rays (Rhinoptera bonasus) are susceptible to ocular disease with their prominent globes, but despite being popular animals housed in aquaria, there is little published information about their normal ocular anatomy and common pathologic ocular findings. A total of 63 live cownose rays (CNR) from three unrelated, separately housed groups had ocular examinations, and 5 adult rays were selected for ocular ultrasound. All examinations were performed out of the water, and most without anesthesia. Clinical findings were described, categorized, and scored by severity. Sixty-two of 63 rays (123 eyes) had clinical abnormalities, including 110 eyes with corneal pathology (mild = 76, moderate/severe = 34) and 74 eyes with intraocular pathology (mild = 44, moderate/severe = 30). Grey-to-white corneal opacities were the most common pathology (n = 58 rays/100 eyes) followed by cataracts (n = 41 rays/58 eyes), then persistent (or dysplastic) pupillary membranes (n = 14 rays/15 eyes). Most pathologic findings appeared inactive, but one aquarium had several CNR with active ocular pathology. There was a significant association between the diagnosis of moderate/severe corneal and intraocular pathology with age (P = 0.008 and P = 0.014, respectively) and weight (P = 0.001 and P = 0.039, respectively), as well as moderate/severe corneal pathology and group sampled (P = 0.03). There were no other significant variables identified. Additionally, histopathology of 14 eyes (11 rays) from two different facilities were examined, with keratitis (n = 8) and uveitis (n = 2) as the most common lesions. This study shows a high prevalence of pathologic ocular findings in cownose ray eyes with heavier adults more likely to be affected than lighter juveniles. Comprehensive ocular evaluation is important in this species and serial ocular exams and future studies should be pursued to monitor ocular disease progression and better understand possible etiologies.

Impact of Long-Term Treatment with Belantamab Mafodotin on Safety and Efficacy Outcomes in Patients with Relapsed/Refractory Multiple Myeloma in DREAMM-3

Introduction: DREAMM-3 (NCT04162210) is a randomized study comparing single-agent belantamab mafodotin, a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, to a standard-of-care regimen, pomalidomide plus dexamethasone (Pd). This post-hoc analysis from the DREAMM-3 trial evaluated the safety and efficacy of long-term treatment (≥52 weeks) with belantamab mafodotin compared with Pd, as well as the effects of dose modifications, in adult patients with relapsed/refractory multiple myeloma (RRMM) at third line of therapy or later. Methods: Patients were randomized (2:1) to belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks (Q3W; 21-day cycle) or pomalidomide 4 mg orally once daily (Days 1-21) and dexamethasone 40 mg (20 mg if &amp;gt;75 years) orally once weekly (28-day cycle). Belantamab mafodotin dose reductions or delays were permitted to manage treatment-related Grade 3-4 adverse events (AEs), or Grade 2 AEs that were worsening or had symptoms lasting &amp;gt;7 days. Following AE resolution to Grade ≤1, belantamab mafodotin treatment could resume with or without dose reduction (to 1.9 mg/kg). If no dose delays occurred, patients could receive a maximum of 17 cycles in 52 weeks, hence 17 cycles was used as a threshold to assess long term safety. Ocular exams were performed prior to dosing belantamab mafodotin Q3W up to Cycle 6, then every 3 months if no significant ocular events were reported. Treatment-related ocular AEs were graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 and per the Keratopathy Visual Acuity (KVA) scale. The KVA scale incorporates corneal examination findings and changes in Snellen-equivalent best corrected visual acuity (BCVA) into a composite grade. Ocular AEs are reported as worst-case post-baseline. Efficacy responses (per 2016 International Myeloma Working Group criteria) were assessed Q3W, regardless of treatment delays. Results: As of September 12, 2022, 50/218 (23%) patients were treated with belantamab mafodotin for ≥52 weeks. AEs were reported in all patients treated with belantamab mafodotin for ≥52 weeks. Grade ≥3 AEs occurred in 82% (n=41); the most frequent were reduced visual acuity (24%), thrombocytopenia (18%), and neutropenia (16%). The majority of AEs reported occurred at or before cycle 17. For the most common (&amp;gt;40%) AEs (any grade), few additional events occurred after cycle 17 (1 new occurrence each of dry eye, reduced visual acuity, eye irritation, and thrombocytopenia after cycle 17). Few infections (any grade) occurred after cycle 17 (COVID-19, n=5; viral infection, n=1; pneumonia influenzal, n=1). No patients permanently discontinued treatment due to AEs considered related to belantamab mafodotin. Ocular AEs were reported in 94% (n=47) of patients treated with belantamab mafodotin for ≥52 weeks. The majority of ocular AEs (n=487) were of Grade 1 or 2 severity (88%) and no ocular AEs led to study treatment discontinuation. At the time of data cutoff, 95% (n=41) of patients experiencing Grade ≥2 KVA events had recovered prior to the end of study treatment exposure (defined as last dose + 20 days). Most patients had a dose modification, and no loss of efficacy was observed. The clinical benefit rate (≥minimal response) in these patients was 90% (45/50) and the median time to best response was 6.3 months (range 0.8-18.8). Median duration of response was not reached (NR; 95% CI 17.9, NR) in the subset of patients treated for ≥52 weeks. At the time of data cutoff, 94% (n=47) patients were alive. Conclusions: In patients who received long-term treatment (≥52 weeks), the safety profile of belantamab mafodotin was consistent with previous reports. Despite the need for belantamab mafodotin dose delays and reductions, no patients discontinued study treatment due to belantamab mafodotin-related AEs. During dose delays, clinical responses were maintained or deepened in most cases, demonstrating that management of AEs using dose modifications did not impact clinical activity. Together, this suggests that dose modifications are highly effective in the management of emerging AEs while allowing for sustained clinical benefit. Funding: GSK (207495). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Evaluation of a Novel Method for the Assessment of Ocular Adverse Events and Associated Functional Impact in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen, has shown promising efficacy and a favorable tolerability profile in the treatment of multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. Keratopathy and Visual Acuity (KVA) scale was used in most belamaf trials, including the pivotal DREAMM-2, to guide belamaf dose modifications. KVA grading is dependent on an ophthalmologist consultation prior to belamaf administration. Herein, we evaluate a novel approach to guide belamaf dosing in transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Part 1 evaluated the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and established that the recommended phase 2 dose (RP2D) is 1.9 mg/kg, initially administered q8w and, depending on toxicity, adjusted to q12w. Part 2 investigates the safety/efficacy of RP2D in Groups A and B, comprised of 15 pts each, and evaluates two different sets of guidelines for the management of OAEs. In Group A, belamaf dosing is guided by the KVA scale; in Group B, dose modifications are determined by the pts' responses on ocular symptoms and their impact on activities of daily living (ADL), captured by the Vision Related Anamnestic (VRA) tool, and by the presence of ≥Grade (Gr) 3 KVA events (BCVA reduced/corneal findings). VRA is a novel, 9-item physician administered questionnaire designed to assess the frequency of ocular symptoms and their impact on vision-related activities. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation, while ocular symptoms are classified by CTCAE v5.0. Herein, we present the OAEs and the clinical activity of the treatment combination for both Groups of Part 2 (cut-off date 05/06/2023). Results By the cut-off date, twenty-four pts [median age: 75.5 years; male: 16 (66.7%)] had received ≥ 1 belamaf dose in Part 2 and were still on treatment. At baseline, most pts had ocular comorbidities. The median belamaf administrations and number of cycles reached were 3.0/2.0 and 6.5/5.5, for Groups A and B, respectively. A meaningful BCVA decline (BCVA &amp;lt;20/50) with at least 3 lines drop in the better seeing eye, was noted in 5/52 (9.6%) and 5/45 (11.1%) assessments, while BCVA ≤20/200 with at least 3 lines drop was noted in 1/59 (1.7%) and 2/51 (3.9%), respectively. Overall, no ≥Gr 3 ocular symptoms were observed, while the most frequent ≥Gr 2 ocular symptom was dry eye (57/110, 51.8%); also, no ≥Gr3 keratopathies were recorded. Among 66/59 VRA assessments, ocular symptoms and ADL impairment, manifesting for &amp;gt;50% of the time (substantial time) in the last 24 hours prior to belamaf administration, were noted in 2 (3.0%)/9 (15.3%) and 2 (3.0%)/7 (11.9%), respectively. Importantly, numerically similar proportions of KVA events and skipped belamaf doses were noted in both Groups (Table 1). Furthermore, although the sample size of the present analysis does not allow conclusions for the VRA test characteristics, it is notable that in all assessments where eyesight difficulties were reported for substantial time, ≥Gr2 KVA events were also recorded, suggesting a potential association between VRA responses and KVA events, that warrants further investigation. Finally, in terms of clinical activity, for the 19 response-evaluable pts (≥2 efficacy assessments), at a median follow-up of 7.4 months the ORR was 90%/100% in Groups A and B (PR/VGPR: 30%/60%; 66.7%/33.3%) with no disease progression observed. Conclusions In this preliminary descriptive analysis, the VRA tool was safe and effective in informing belamaf dose adjustments in the extended dosing schedule. Recruitment in Part 2 is ongoing and, as data accumulates, future analyses will provide further insight on the potential association of the VRA tool with KVA events, which may eliminate the need for an ophthalmic exam prior to belamaf dosing.

Long-Term Safety and Efficacy Results of Belantamab Mafodotin Plus Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: An Updated Part 1 Analysis from the Phase 1/2 Belard Trial

Introduction The preferred upfront treatment of transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM) consists of the combination of lenalidomide and dexamethasone (Rd) with a third antimyeloma agent of a different mechanism of action (e.g., proteasome inhibitors or anti-CD38 monoclonal antibodies). Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting BCMA, has shown efficacy in pretreated MM pts, while preclinical data demonstrate synergy between belamaf and lenalidomide, with no overlapping toxicities. Thus, there is a strong rationale for investigating the belamaf-Rd triplet in TI NDMM pts. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Eligible are adult pts with ECOG PS 0-2 and adequate organ function. Part 1 evaluates the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and establishes the recommended phase 2 dose (RP2D). In this part, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation. Ocular symptoms are classified by CTCAE v5.0, while the Ocular Surface Disease Index (OSDI) captures dry eye disease and activities of daily living (ADL).Herein, we present updated safety and efficacy results of all Part 1 pts with an extended follow-up time (cut-off date 05/06/2023). Results Of the 36 pts [median age: 72.5 years; male: 19 (53%)] in Part 1, 29 (81%) are still on treatment, while 7 (19%) have discontinued [6 pts due to belamaf-unrelated fatal events: (COVID-19: 1/1/2; Pneumonia: 1/1/0, for cohorts 2.5/1.9/1.4 respectively); 1 pt withdrew consent]. The median belamaf administrations and number of cycles reached were 6/7/7 and 20.0/22.5/20.0, for the respective cohorts. The most common (≥10% of pts) non-ocular ≥ Gr3 treatment-emergent adverse events were fatigue (21 pts, 58%; [7 (58%)/7 (58%)/7 (58%)]), diarrhoea (8 pts, 22%; 2 (17%)/3 (25%)/3 (25%)]), rash (6 pts, 17%; [2 (17%)/2 (17%)/2 (17%)]), COVID-19 (5 pts, 14%; [2 (17%)/1 (8%)/2 (17%)]) and insomnia (4 pts, 11%; 0/4 (33%)/0]) , while no ≥Gr3 thrombocytopenias and infusion-related reactions were reported. Regarding ≥Gr3 infections other than COVID-19, pneumonia was reported for 3 (8%) pts [1/1/1 (8%)] and lower respiratory tract infection for 1 (3%) pt [0/0/1(8%)]. Regarding ocular adverse events (OAEs), among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4, a meaningful BCVA decline (BCVA &amp;lt;20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%), while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. Across all cohorts, the most frequently reported ≥Gr 3 ocular symptom was decreased vision (26/665, 4%), while ≥Gr3 keratopathy was noted in &amp;lt;2% of assessments. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the ADL category were 6 (3%)/4 (2%)/3 (2%). The overall response rate was 100% across all cohorts: More specifically CR or better was achieved by 7 (58%)/6 (50%)/6 (50%), VGPR by 3 (25%)/5 (42%)/3 (25%) and PR by 2 (17%)/1 (8%)/3 (25%) pts in cohorts 2.5/1.9/1.4, with a median time to first response of 1 month. Finally, at a median follow-up of 20.3 months, no disease progression was observed, median PFS and median time to progression were not reached ( Figure 1) and responses continue to deepen across all cohorts. Conclusions Over an extended follow-up period, the belamaf-Rd triplet has proven a safe and effective combination for the upfront treatment of TI NDMM pts, with no long-term safety signals. Furthermore, the extended dosing schedule for belamaf had a minimal impact in vision-related functioning, as very low rates of meaningful BCVA decline and “most/all” OSDI responses were noted across all cohorts, with a rapid time to resolution. Meanwhile, a very promising clinical activity is observed, with rapid, deep and durable responses across all dose levels. Consequently, after validation with bigger pt numbers, this novel combination may well be a very attractive frontline option for this vulnerable and difficult-to-treat pt population.

Cataracts after Ophthalmic andNonophthalmic Trauma Exposure inService Members, U.S. Armed Forces.

IntroductionWe aimed to identify injury-related risk factors for secondary cataract incidence after eye and brain injury and polytrauma. We also examined the effect of direct and indirect eye injury management on cataract diagnosis and treatment. Prevention or mitigation strategies require knowledge of the causes and types of combat injuries, which will enable more appropriate targeting of resources toward prevention and more efficient management of such injuries. Data were gathered from the Military Health System using the Military Health System Management and Analysis Reporting Tool (M2) between 2017 and 2021 from inpatient and outpatient Service Members (SMs) (active duty and National Guard). The date of the first cataract diagnosis was tracked to estimate the annual incidence rate, and it was longitudinally linked to any prior diagnosis of ocular trauma (OT), traumatic brain injury (TBI), or polytrauma to calculate the relative risk. International Classification of Disease codes, 10th Revision, were used to identify those diagnosed with cataracts, TBI, and polytrauma. Defense and Veterans Eye Injury and Vision Registry data were used to examine SMs who sustained ocular injuries from 2003-2020 and who may have had cataract surgery following a cataract diagnosis. The relative risk of traumatic cataract formation from OT, TBI, and polytrauma are 5.71 (95% CI, 5.05-6.42), 2.32 (95% CI, 2.03-2.63), and 8.95 (95% CI, 6.23-12.38), respectively. Traumatic cataracts in SMs more commonly result from open-globe injuries (70%) than closed-globe injuries (30%). By specific sub-injury type, traumatic cataracts occur most frequently from intraocular foreign bodies (22%). More than 400 patients in the cohort suffered from TBI and traumatic cataracts, more than 300 from OT and cataracts, and more than 20 from polytrauma and cataracts. The battlefield is the riskiest environment for trauma exposure, with 62% of OT occurring in combat. There was a statistically significant difference between the mean visual acuity value before cataract surgery (M = 1.17, SD = 0.72) and the mean visual acuity value after cataract surgery (M = 0.44, SD = 0.66, P < .001). Traumatic cataracts often occur in SMs who sustain ocular injuries. New to the literature is that relationships exist between traumatic cataract formation and nonglobe trauma, specifically TBI and polytrauma. Ocular injury calls for an ophthalmic examination. A low threshold should exist for routine ocular exam consultation in the setting of TBI and polytrauma. Separately, polytrauma patients should undergo a review of systems questions, particularly questions about the ocular and visual pathways. A positive response to screening warrants further investigation of possible ocular pathology, including traumatic cataract formation. Cataract surgery is an effective treatment in improving the vision of SMs who suffer from traumatic cataracts. Constant effort must be made to limit occurrences of occupation-related traumatic cataracts.

A review of pursuit and saccadic eye movements and their utility in stroke

The head impulse-nystagmus-test of skew (+ hearing) or HINTS+ exam is a well-established clinical bedside test used in evaluating whether patients with the acute vestibular syndrome have features concerning for a central etiology (e.g., stroke). There are other components of the ocular motor exam that are helpful in the acute setting, including smooth pursuit and saccades. We discuss the anatomy and physiology of the saccade and smooth pursuit pathways from the cortex to the infratentorial region in the context of anterior and posterior circulation strokes in general but with a particular emphasis on distinct vestibular stroke syndromes. For each stroke localization, we review the vascular supply and the expected findings on the HINTS+ exam and correlate this with the expected findings on the smooth pursuit and saccade exams to aid in bedside diagnosis.

Ocular posterior segment microstructural and microvascular morphological changes in protein supplement-consuming bodybuilders

BackgroundTo determine the effects of protein supplement (whey protein powder (PP)) on retinal, choroidal and optic nerve head (ONH) microstructure and microvascular morphology in healthy bodybuilders. MethodsThis cross-sectional study included 23 male adults (consumers, 23 right eyes) who had been routinely consuming whey PP for bodybuilding purposes for ≥ 3 months, and 21 age- and gender-matched healthy volunteers (non-consumers, 21 right eyes) who also attended the gym but did not consume any nutritional supplements. Participants underwent standard ocular exams, enhanced depth imaging optical coherence tomography (EDI OCT), and optical coherence tomography angiography (OCTA) after ≥ 8 h of rest and fasting. ResultsWhey PP was consumed for a median of 9.5 (6–12) months. Whey PP consumers had a median age of 22 (21–22) years, while non-consumers had 21 (20–22) years (p = 0.067). Whey PP consumers had greater microstructural thickness than non-consumers, with subfoveal choroidal thickness (301.40 ± 38.91 versus 278.12 ± 33.58 µm; p = 0.035) being significantly different but not central macular thickness (270.55 ± 24.60 versus 265.85 ± 12.44 µm; p = 0.402). Despite a non-significant difference in superficial and deep capillary plexus vascular densities (VDs), whey PP consumers had relatively lower VDs than non-consumers in all macular regions (p > 0.05). Despite this, whey PP consumers displayed greater ONH VDs, as well as higher global RNFL thickness (116.75 ± 10.41 versus 114.50 ± 11.70 µm) than non-consumers (p > 0.05). ConclusionProtein supplements, particularly whey PPs, appear to be associated with different changes in the retina and choroid, as well as ONH microstructural and microvascular morphology, implying that paying attention to these clinical aspects when performing ocular tests in bodybuilders who consume nutritional supplements could be critical.

The Association Between the Severity of Trachomatous Scarring and Trachomatous Trichiasis Severity in Surgical Patients in Tanzania

ABSTRACT Purpose To determine the association between the severity of trachomatous conjunctival scarring (TS) of the upper eyelid conjunctiva and trachomatous trichiasis (TT) severity in TT surgical patients. Methods A cross-sectional study was conducted amongst adults with TT who were referred to surgical camps in Bahi District, Tanzania, for TT surgery. Participants underwent ocular examination. The presence and severity of TS was evaluated in photographs of the everted upper eyelid. TT severity was assessed at the time of the ocular exam based on the number of lashes touching the globe and/or evidence and extent of epilation. Ordinal logistic models were used to examine the association between the severity of TS and TT severity. Results A total of 627 eyes of 388 participants were included. Mean age was 65 years (ranging from 21–98), 81% were females, and 62% had bilateral TT. 93% of eyes with any TT had at least moderate TS; 62% of eyes had severe TS. An increase in TS severity was associated with an increase in the severity of TT. Using as a reference eyes with none to mild TS, in eyes with moderate TS the odds of increased severity of TT was 1.30 (95% CI 0.67–2.51), in eyes with severe TS the odds was 4.20 (95% CI 2.23–7.92). Conclusion In cases of trachomatous trichiasis presenting for surgery, the severity of TT was significantly associated with the severity of TS with almost all cases of TT having moderate or severe scarring.

Diagnostic Accuracy of Disc Damage Likelihood Scale and Cup-To-Disc Ratio for Diagnosis of Glaucoma

Purpose: To find the diagnostic accuracy of Disc Damage Likelihood Scale (DDLS) and cup-to-disc ratio (CDR) for diagnosis of glaucoma taking CCT adjusted IOP and characteristic visual filed defects with corresponding OCT-ONH changes as standard. Study Design: Comparative, cross-sectional. Place and Duration of Study: Department of Ophthalmology, Mayo Hospital, Lahore, from August 2020 to February 2021. Methods: Three hundred and nine patients were enrolled after taking informed consent. Demographic data was obtained, and patients underwent complete ocular exam including DDLS and CDR, Slit-lamp biomicroscopy, gonioscopy and Intraocular pressure (IOP). Central corneal thickness, visual fields and OCT ONH was done. The patient was said to have glaucoma if his CCT adjusted IOP was greater than 21 mmHg, visual field defects and OCT changes. It was compared with CDR and DDLS, which was taken as suggestive of glaucoma with scores greater than 5. Results: Mean age of patients was 54.82 ± 9.29 years, 108 (34.95%) were males. The sensitivity, specificity and diagnostic accuracy of DDLS for detection of glaucoma was 78.57%, 84.97% and 80.91% and the sensitivity, specificity and diagnostic accuracy of CDR for detection of glaucoma was 82.14%, 49.56% &amp; 70.23% taking CCT adjusted IOP and characteristic visual field defects with corresponding OCT changes as standard. Conclusion: Disk Damage likelihood scale is useful, cost effective and has higher accuracy to detect glaucomatous damage as compared to cup-to-disc ratio for diagnosis of glaucoma taking CCT adjusted IOP and characteristic visual field defects with corresponding OCT changes as standard.

Differentially Expressed Tear Proteins in Sjögren's Syndrome Keratoconjunctivitis Sicca.

The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls. Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire in dry eye (SANDE) scores were collected for all patients. Two hundred fifty-three of the 507 tear proteins analyzed were significantly different in patients with SS compared to controls. Two hundred forty-one if the proteins were upregulated and 12 were downregulated. One hundred eighty-one differentially expressed proteins were significantly correlated with all four clinical parameters: TBUT, CF staining, CJ staining, and SANDE score. These findings indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip. The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls. The upregulated tear proteins correlated with clinical measures of dry eye symptoms and disease severity. Tear proteins could serve as important biomarkers for studying pathogenesis and in clinical diagnosis and management of SS KCS.

Correlation between cognitive tests with scales, vestibular exam and questionnaires for dizziness in the elderly

AbstractBackgroundThe vestibular system interacts with various cognitive functions, including spatial navigation processes, spatial perception, body representation, mental images, attention, memory, risk perception and social cognition. Studies inform that cognitive impairment is an important risk factor for changes in motor performance and body balance.MethodCross‐sectional, observational and analytical study. The sample consisted of 38 elderly people with vestibular dysfunction confirmed by cervical and ocular VEMP exams and/or Video Head Impulse Test (v‐HIT). The procedures of this research were approved by the Ethics Committee of the University under the number CAAE 49714221.0.0000.5149. All participants signed the Informed Consent Form (FICF). Cognitive tests were applied in a room with the patient seated. Paper and pencil were used and all cognitive tests, scales and vestibular exams were performed by the same trained researcher. Analysis using the SPSS program ‐ version 22.0. The distribution of variables was verified using the Kolmogorov‐Smirnov test. Correlation analysis was performed using the Pearson test. We adopted a significance level of 5% (p&lt;0.05).ResultA positive correlation was found between the MMSE with the gain of the left semicircular canal and negative with the asymmetry of the lateral canals. The Frontal Assessment Battery was negatively correlated with the VAS and positively correlated with the left semicircular canal. The Pfeffer questionnaire showed a positive correlation with the VAS, DHI and its functional and emotional subscales, in addition to a negative correlation with the Berg balance scale. The geriatric depression scale correlated negatively with the VAS and the Berg balance scale and positively correlated with the total DHI and its functional and emotional subscales.ConclusionIn this study, cognitive aspects, depressive symptoms and functionality were correlated with decreased gain of the left semicircular canal, greater asymmetry of the lateral canals, higher scores on the visual analogue scale, greater impact of dizziness on quality of life and greater risk of falls.

715 Ocular Complications of Facial Burns in the Pediatric Population

Abstract Introduction Pediatric burns commonly involve the face and periocular areas, with a risk of impairing vision. The aim of this study is to characterize ocular injuries in burn patients and identify the patients at most risk of ocular complications. Methods This study is a retrospective review within a single academic, urban pediatric burn center. All burn patients under 18 years of age admitted from January 2010 to December 2020 with periorbital or ocular involvement were included. Variables analyzed included patient demographics, burn characteristics, presence of ophthalmology consultation, ocular exam findings, follow up time period, and early and late ocular complications. Results In the study period, 2,781 patients were admitted to our burn center, 300 of whom had facial burns involving the eyes and/or eyelids. Etiologies of burn injuries were as follows: 112 (37.5%) scald, 80 (26.8%) flame, 35 (11.7%) contact, 31 (10.4%) chemical, 28 (9.4%) grease, and 13 (4.3%) friction. Overall, 70.9% of patients with ocular burns received an ophthalmology consult. Of these patients, 61.5% had periorbital swelling and 39.8% had corneal injuries. Of the 207 patients who were followed as inpatients by ophthalmology, only 61 (29.5%) presented for a follow-up visit, as recommended, 6 of which had serious ocular sequelae including ectropion, entropion, symblepharon, and corneal decompensation, and 4 of whom had a firework-related injury. Conclusions While burns involving the ocular surface and eyelid margins are infrequent overall, they can lead to long-term sequelae. Ophthalmology consultation is critical, particularly in the setting of chemical and firework-related injury. As ocular and periocular burns can cause immediate as well as delayed sequelae, ophthalmologic evaluation is a key component of assessment. Applicability of Research to Practice This paper characterizes ocular injuries in pediatric patients with facial burn injuries and identifies patients most at risk for ocular complications. We believe this will be valuable for many burn researchers and clinicians in order to better identify patients who could benefit from ophthalmologic evaluation and those at risk for both immediate as well as delayed sequelae from periocular burns.

Optimal Image Gain Intensity of Point-of-care Ultrasound when Screening for Ocular Abnormalities in the Emergency Department.

Point-of-care ultrasound (POCUS) plays a pivotal role in evaluating ocular complaints in the emergency department (ED). The rapid and non-invasive nature of ocular POCUS makes it a safe and informative imaging modality. Previous studies have investigated using ocular POCUS to diagnose posterior vitreous detachment (PVD), vitreous hemorrhage (VH), and retinal detachment (RD); however, there are few studies that assess image optimization techniques and how they impact the overall accuracy of ocular POCUS. We performed a retrospective review of ED patients who received ocular POCUS examinations and ophthalmology consultations as part of their evaluation for eye complaints at our urban, Level I trauma center ED from November 2017-January 2021. Of 706 exams, 383 qualified for the study. In this study we primarily investigated how stratified gain levels impact the accuracy of ocular POCUS for detection of any posterior chamber pathology and, secondarily, whether stratified gain levels impact the accuracy of detecting RD, VH, and PVD specifically. The images were found to have an overall sensitivity of 81% (76-86%), specificity of 82% (76-88%), positive predictive value (PPV) of 86% (81-91%), and negative predictive value (NPV) of 77% (70-83%). Images acquired with a gain of (25, 50] had a sensitivity of 71% (61-80%), specificity of 95% (85-99%), PPV of 96% (88-99%), and NPV of 68% (56-78%). Images acquired with a gain of (50, 75] had a sensitivity of 85% (73-93%), specificity of 85% (72-93%), PPV of 86% (75-94%), and NPV of 83% (70-92%). Images acquired with a high gain (75, 100] had a sensitivity of 91% (82-97%), specificity of 67% (53-79%), PPV of 78% (68-86%), and NPV of 86% (72-95%). In the ED setting, high (75, 100] gain on ocular POCUS scanning has a higher degree of sensitivity for detecting any posterior chamber abnormality, as compared to low (25, 50] gain levels. Thus, incorporating the use of high gain for ocular POCUS exams produces a more effective tool for ocular pathologies in acute care settings and may be particularly valuable in resource-limited settings.

Ocular Complications of Facial Burns in the Pediatric Population.

Pediatric ocular burns carry a risk of permanent vision impairment. This study identifies risk factors that place these patients at high risk of permanent visual complications. A retrospective review was conducted in our academic urban pediatric burn center. All 300 patients under 18 years of age admitted from January 2010 to December 2020 with periorbital or ocular thermal injuries were included. Variables analyzed included patient demographics, burn characteristics, ophthalmology consultation, ocular exam findings, follow up time period, and early and late ocular complications. Etiologies of burn injuries were as follows: 112 (37.5%) scald, 80 (26.8%) flame, 35 (11.7%) contact, 31 (10.4%) chemical, 28 (9.4%) grease, and 13 (4.3%) friction. Overall, 207 (70.9%) patients with ocular burns received an ophthalmology consult. Of these patients, 61.5% had periorbital cutaneous burns and 39.8% had corneal injuries, and only 61 (29.5%) presented for a follow-up visit. Ultimately, six had serious ocular sequelae, including ectropion, entropion, symblepharon, and corneal decompensation. While thermal burns involving the ocular surface and eyelid margins are relatively infrequent overall, they carry a small risk of serious to long-term sequelae. Recognizing those at greatest risk, and initiating appropriate early intervention is critical.