Disparities Between Clinical Trial Recruitment and Real-World Demographics in Macular Edema Secondary to Retinal Vein Occlusion.

PURPOSE: Clinical trial cohorts frequently differ demographically from the overall population receiving treatment for the condition under study. Our study describes the racial, ethnic, and gender composition of the cohorts of retinal vein occlusion (RVO) macular edema (ME) clinical trials and compares this to the racial, ethnic, and gender composition of patients undergoing treatment for ME secondary to RVO from the (Intelligent Research in Sight) IRIS Registry. DESIGN: Retrospective observational case series Subjects: Participants in RVO-ME clinical trials that met the following inclusion criteria: conducted in the United States of America, Phase III completed, data reported between January 1, 2000, and January 1, 2020, and demographic information reported with results. METHODS: This study identified clinical trials by searching PubMed with the following search terms; "retinal vein occlusion" and "clinical trial" and by searching ClinicalTrials.gov with the search term "retinal vein occlusion." MAIN OUTCOME MEASURES: The primary outcome was the enrollment fraction defined as the number of trial enrollees divided by the reference sample size of RVO patients undergoing treatment for ME from published IRIS Registry (Intelligent Research in Sight) data. Enrollment fraction was compared between different races, ethnicities, and genders. RESULTS: Eight clinical trials met our inclusion criteria. Compared to the enrollment fraction of 7.69% among Whites, lower enrollment fractions were found in Black patients (4.32%, odds ratio [OR] 0.541, confidence interval [CI] 0.468-0.626, P < .001) and Hispanic patients (3.38%, OR 0.420, CI 0.351-0.503, P < .001), and higher enrollment fraction in Asian patients (10.68%, OR 1.436, CI 1.207-1.708, P < .001). Men were more likely to enroll in the clinical trials compared to women (enrollment fraction, 7.69% vs 5.77%, respectively, OR 1.364, CI 1.273-1.462, P < .001). CONCLUSIONS: RVO-ME clinical trials have a higher relative proportion of Asian, White and male subjects when compared to the population undergoing treatment for ME secondary to RVO. Further efforts should encourage clinical trial recruitment that is reflective of the RVO population undergoing treatment for ME to ensure generalizability of clinical trial results.

Google Search Trends to Assess Public Interest and Concern About Pegcetacoplan for the Treatment of Geographic Atrophy.

OBJECTIVE: To assess global trends in interest surrounding the newly Food and Drug Administration (FDA)-approved treatment for geographic atrophy, (GA), Syfovre (pegcetacoplan), and related searches. METHODS: We utilized Google Trends, in order to gauge the public interest in Syfovre from October 16, 2022, to October 8, 2023. RESULTS: Notable spikes in relative search volumes (RSV)s for "Syfovre" were observed in mid-to-late February 2023, and in March and April 2023, coinciding with the drug's FDA approval and introduction to the market. Of the various side effects, retinal vasculitis garnered the most significant attention, with a sharp rise in RSV in mid-July 2023. Geographic variation was evident, with the highest RSVs for "Syfovre" originating from users on the East Coast. CONCLUSION: Google Trends proves to be a useful tool for gaining insight into public interest in pegcetacoplan as a treatment for GA. [Ophthalmic Surg Lasers Imaging Retina 2024;55:452-460.].

Pseudoxanthoma elasticum-associated angioid streaks near a scleral buckle.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

Alternative Techniques To Remove Retained Silicone Oil Droplets On IOLs.

BACKGROUND/PURPOSE: To describe several modified approaches to remove retained silicone oil droplets on intraocular lens (IOLs). METHODS: Four novel techniques for removing retained silicone oil droplets on IOLs were described. RESULTS: All four techniques led to an improved IOL with a good view to the posterior segment. No intraoperative or long-term postoperative complications have been seen in any of these eyes. These modified approaches are safe, efficient, low cost, and use existing vitreoretinal operating room supplies to add to the vitreoretinal surgeon's armamentarium to clear retained IOL silicone droplets. CONCLUSION: It is advocated for having multiple techniques at the disposal of the vitreoretinal surgeon to address retained silicone oil on IOLs. Being able to use multiple techniques may not be superior than a single approach but is often necessary to accomplish the surgical goal of removing these adherent droplets.

THE STATE OF PEDIATRIC RETINAL DETACHMENT SURGERY IN THE UNITED STATES: A Nationwide Aggregated Health Record Analysis.

PURPOSE: In this study, the authors aimed to identify the demographics of retinal detachment in children in the United States and to report the treatment modalities chosen by vitreoretinal surgeons and associated outcomes. METHODS: This was a multicenter cohort analysis of the Vestrum Health LLC Database (Naperville, IL). Children (1-17 years) with rhegmatogenous retinal detachment, as identified by ICD10 and CPT codes, between January 2015 and August 2021 were enrolled. Demographic, comorbidity, visual acuity, and treatment modality data were analyzed. RESULTS: A total of 168,152 RRDs were identified, of which 2,200 (1.3%) were aged 1 to 17 years. The mean age was 12.7 years, and 821 (37%) were women. The prevalence of rhegmatogenous retinal detachment increased with age ( P = 0.009). Associated comorbidities included myopia (17.3%), ocular trauma (7.5%), and history of prematurity (5.7%). Laser retinopexy alone was used as the initial treatment modality in 19%, primary vitrectomy in 23%, primary scleral buckle in 25%, and vitrectomy with scleral buckle in 33%. The single surgery success rate for all procedures was 73.3%. Of the incisional surgical modalities, primary scleral buckling had the best single surgery success rate (79.0%) compared with vitrectomy alone (64.5%) and vitrectomy with scleral buckle (67.2%) ( P < 0.001 and P = 0.004, respectively). Younger age resulted in worse SSSR overall (coefficient = 0.151, R 2 = 0.746, P = 0.027). CONCLUSION: Rhegmatogenous retinal detachments in children increased with age. Myopia, trauma, and history of retinopathy of prematurity were common risk factors. Treatment techniques varied, but primary scleral buckling had the best anatomical and visual outcomes.

Primary Synovial Sarcoma of the Orbit: A Case Report and Update on Diagnostic Techniques.

Synovial sarcoma is a malignant mesenchymal tumor that most commonly occurs in the deep soft tissue of the extremities in adolescents and young adults. Primary periocular synovial sarcoma is extremely rare with only 11 previously reported cases. We describe a 23-year-old woman who presented with a 1-year history of painful, progressive right upper eyelid swelling. She was subsequently found to have a superomedial orbital mass on CT scan. Pathologic evaluation revealed a spindle cell neoplasm with SS18 (SYT) rearrangement by fluorescence in situ hybridization studies, consistent with a monophasic synovial sarcoma. This case describes the clinical, radiographic, histopathologic, and molecular cytogenetic features of this rare orbital neoplasm, with an emphasis on the emerging diagnostic techniques and novel therapies.

Exenteration and Adjuvant Radiotherapy for Primary Carcinosarcoma of the Anterior Orbit: A Case Report.

Carcinosarcoma is a malignant mixed tumor composed of epithelial and mesenchymal components which arises in a variety of tissues, including, in rare cases, the orbit. A 75-year-old male with a history of basal cell carcinoma of the left medial canthus, previously treated with surgical resection and adjuvant radiation therapy, presented with a recurrent 3 cm nodule of the left medial canthus. He underwent surgical resection of the left superior and inferior eyelid with pathology revealing invasive squamous cell carcinoma of upper and lower eyelids with deep orbital tissue involvement and undifferentiated pleomorphic sarcoma involving the dermis and periosteum, consistent with carcinosarcoma. Orbital exenteration was subsequently performed. He successfully underwent adjuvant stereotactic body radiation therapy 30 Gy in 5 fractions with no significant side effects. Follow-up MRI revealed posttreatment changes without evidence of recurrent disease.

The Impact of Physician Face Mask Use on Endophthalmitis After Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To evaluate the effect of physician face mask use on rates and outcomes of postinjection endophthalmitis. DESIGN: Retrospective, comparative cohort study. METHODS: Setting: Single-center. StudyPopulation: Eyes receiving intravitreal anti-vascular endothelial growth factor injections from July 1, 2013, to September 1, 2019. INTERVENTION: Cases were divided into "Face Mask" group if face masks were worn by the physician during intravitreal injections or "No Talking" group if no face mask was worn but a no-talking policy was observed during intravitreal injections. MainOutcomeMeasures: Rate of endophthalmitis, visual acuity, and microbial spectrum. RESULTS: Of 483,622 intravitreal injections administered, 168 out of 453,460 (0.0371%) cases of endophthalmitis occurred in the No Talking group, and 9 out of 30,162 (0.0298%) cases occurred in the Face Mask group (odds ratio, 0.81; 95% confidence interval, 0.41-1.57; P = .527). Sixteen cases of oral flora-associated endophthalmitis were found in the No Talking group (1 in 28,341 injections), compared to none in the Face Mask group (P = .302). Mean logMAR visual acuity at presentation in cases that developed culture-positive endophthalmitis was significantly worse in the No Talking group compared to the Face Mask group (17.1 lines lost from baseline acuity vs 13.4 lines lost; P = .031), though no difference was observed at 6 months after treatment (P = .479). CONCLUSION: Physician face mask use did not influence the risk of postinjection endophthalmitis compared to a no-talking policy. However, no cases of oral flora-associated endophthalmitis occurred in the Face Mask group. Future studies are warranted to assess the role of face mask use to reduce endophthalmitis risk, particularly attributable to oral flora.

Ocular adnexal manifestations of neuroendocrine neoplasms: a case report and a major review.

PURPOSE: To describe a patient with orbital neuroendocrine neoplasm (NEN)/carcinoid tumor and to review the clinical presentation, systemic work-up, histopathologic features, and outcome of all previously reported ocular adnexal (OA) NENs. METHODS: A systematic literature review. PubMed/MEDLINE and Google Scholar databases were searched for all well-documented cases of OA NENs. RESULTS: Final analysis yielded 94 patients with OA NENs, 50 females (53%) and 44 (47%) males with an average age of 63 years (range 14-86). Of 91 patients with known information, the most common presenting signs were proptosis (56/91, 61%) and visual disturbances (42/91, 47%), induced by a mass most commonly associated with an extraocular muscle (49/63, 78%). The majority of tumors (88/94, 94%) were metastases, most commonly from the gastrointestinal tract (52/88, 59%). OA NEN metastasis presented following detection of primary tumor in 73/94 (78%) patients (median time to metastasis 36 months, range 0-288 months) and as an initial manifestation of disease in 15/94 (16%) patients (median time to primary detection 18 months, range 1-108 months). Systemic work-up included extra-OA NEN biopsy (37/54, 69%), multimodal imaging (42/54, 78%), and other laboratory studies (32/54, 59%). Resection with or without adjuvant chemotherapy, radiotherapy, and biologics was the most common intervention for OA NENs (36/82, 44%). Of 67 patients with available follow-up, the median survival was 108 months (95% CI 55-161 months) and the absolute 5-year survival rate was 68%. CONCLUSIONS: OA NENs are almost exclusively metastases and can precede detection of primary tumor by many months, requiring appropriate diagnostic work-up.

Amelanotic Ciliochoroidal Melanoma in a Patient with Oculocutaneous Albinism.

To report a case of amelanotic ciliochoroidal melanoma in a patient with oculocutaneous albinism. A 76-year-old Caucasian male with a past medical history of oculocutaneous albinism and recurrent urothelial carcinoma was found to have a mass in the left eye, suspicious for ciliochoroidal melanoma. On examination, visual acuity was 20/400 in both eyes (OU). External examination showed iris transillumination defects. Funduscopic examination OU revealed blonde fundus, optic nerve hypoplasia, and foveal hypoplasia, confirmed on optical coherence tomography. Funduscopic examination of the left eye revealed an inferonasal amelanotic ciliochoroidal mass, measuring 12.0 mm × 13.0 mm × 8.8 mm. There was visible intrinsic tumor vasculature and overlying subretinal fluid. B-scan ultrasonography demonstrated a hypoechoic, dome-shaped mass. The clinical and imaging features were consistent with amelanotic ciliochoroidal melanoma. The patient was treated with iodine-125 plaque radiotherapy. At the 4-month follow-up, the tumor demonstrated regression from 8.8 mm to 3.2 mm in thickness. Despite the apparent lack of uveal pigmentation, patients with oculocutaneous albinism can develop uveal melanoma.

Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture.

PURPOSE: To determine the personalized rate of uveal melanoma-related metastasis on the basis of individual tumor cytogenetic profile. DESIGN: Retrospective case series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine-needle aspiration biopsy (FNAB) for DNA amplification and whole genome array-based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME MEASURES: Melanoma-related metastasis. RESULTS: The mean patient age was 57 years, and most were white (1026/1059, 97%). The melanoma involved the choroid (938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19% being macular in location. The mean largest basal diameter was 11 mm (median, 12 mm; range, 3-24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1-20 mm). On the basis of individual chromosomal mutations, risk for metastasis was increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001), 3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss (HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan-Meier estimate for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for 6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE), and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of personalized cytogenetic profiles, Kaplan-Meier estimates (1, 3, and 5 years) for melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and 8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6 disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]), respectively. CONCLUSIONS: Risk for melanoma-related metastasis strongly correlates with personalized cytogenetic profiles, with 5-year Kaplan-Meier estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3 complete monosomy, 6 disomy, and 8q gain.

Cytogenetic Abnormalities in Uveal Melanoma Based on Tumor Features and Size in 1059 Patients: The 2016 W. Richard Green Lecture.

PURPOSE: To determine the risks for altered cytogenetic profile based on melanoma features and size. DESIGN: Retrospective case series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine-needle aspiration biopsy (FNAB) of tumor for DNA amplification and whole genome array-based assay. MAIN OUTCOME MEASURES: Risk for cytogenetic abnormalities based on features and size: small (≤3 mm thickness), medium (>3-<8 mm), and large (≥8 mm). RESULTS: Of 1059 patients with uveal melanoma sampled for status of chromosomes 3, 6, and 8, comparison (normal [disomy] chromosomes 3, 6, and 8 vs. any 3, 6, or 8 abnormality) revealed differences in mean age (55 vs. 58 years, P = 0.018), ocular melanocytosis (1% vs. 5%, P = 0.027), mean visual acuity (VA) (20/30 vs. 20/50, P = 0.011), poor VA (≤20/200) (9% vs. 15%, P = 0.041), ciliary body location (5% vs. 11%, P < 0.001), extramacular location (73% vs. 87%, P < 0.001), increased mean distance to optic disc (3.3 vs. 5.0 mm, P < 0.001) and foveola (3.1 vs. 4.7 mm, P < 0.001), and increased mean basal diameter (9.8 vs. 12.6 mm, P < 0.001) and thickness (3.8 vs. 5.9 mm, P < 0.001). Tumors classified as small, medium, and large showed abnormalities with loss of disomy of chromosomes 3 (35%/52%/65%), 6 (15%/34%/51%), and 8 (19%/41%/69%), respectively. By comparison (medium/large vs. small melanoma), the odds ratio (OR) included complete monosomy 3 (3.09, P < 0.001), partial monosomy 3 (1.44, P = 0.053), 6p gain (3.78, P < 0.001), 6q gain (1.37, P = 0.537), 6p loss (2.52, P = 0.410), 6q loss (12.61, P < 0.001), 8p gain (6.16, P < 0.001), 8p loss (6.04, P < 0.001), and 8q gain (4.87, P < 0.001). For chromosome 3 monosomy, the OR was highest for ciliary body location (8.17, P < 0.001), tumor thickness ≥8 mm (2.70, P < 0.001), tumor base ≥10 mm (2.59, P < 0.001), and age ≥60 years (1.83, P < 0.001). For chromosome 8p loss, the OR was highest for ciliary body location (53.91, P = 0.008), ocular melanocytosis (3.95, P = 0.038), and thickness ≥8 mm (5.14, P < 0.001), whereas for 8q gain, the OR was highest for ciliary body location (102.87, P = 0.001), thickness >8 mm (4.44, P < 0.001), and ocular melanocytosis (2.75, P = 0.049). CONCLUSIONS: Increasing melanoma size demonstrates greater cytogenetic alterations. Alterations in chromosome 8 show unique correlation with melanocytosis. This suggests that prompt management of small melanoma might reduce chromosomal instability and could improve overall patient survival.

Evolution of focal choroidal excavation underlying combined hamartoma of the retina and retinal pigment epithelium in a child.

Combined hamartoma of the retina and retinal pigment epithelium (RPE) is a benign tumor seen mostly in children. Enhanced-depth imaging optical coherence tomography (OCT) of these tumors often shows an epiretinal membrane, tangential traction, disorganization of the retinal layers, and underlying uniform choroidal thinning. We describe the evolution over 9 years of focal choroidal excavation, a novel finding on OCT characterized as a "microstaphyloma," in a girl with combined hamartoma of the retina and RPE.

Choroidal melanoma in children: be aware of risks.

The authors describe a case of choroidal melanoma in a 13-year-old girl treated with plaque brachytherapy. Uveal melanoma is reported in all age groups but tends to manifest itself in adults more often than children. Childhood (< 20 years) uveal melanoma represents 1% of all cases. Clinical features and treatment options in childhood melanoma are discussed.

Barrier immune effectors are maintained during transition from nurse to forager in the honey bee.

Foragers facilitate horizontal pathogen transmission in honey bee colonies, yet their systemic immune function wanes during transition to this life stage. In general, the insect immune system can be categorized into mechanisms operating at both the barrier epithelial surfaces and at the systemic level. As proposed by the intergenerational transfer theory of aging, such immunosenescence may result from changes in group resource allocation. Yet, the relative influence of pathogen transmission and resource allocation on immune function in bees from different stages has not been examined in the context of barrier immunity. We find that expression levels of antimicrobial peptides (AMPs) in honey bee barrier epithelia of the digestive tract do not follow a life stage-dependent decrease. In addition, correlation of AMP transcript abundance with microbe levels reveals a number of microbe-associated changes in AMPs levels that are equivalent between nurses and foragers. These results favor a model in which barrier effectors are maintained in foragers as a first line of defense, while systemic immune effectors are dismantled to optimize hive-level resources. These findings have important implications for our understanding of immunosenescence in honey bees and other social insects.