Radiation and systemic immunotherapy for metastatic uveal melanoma: a clinical retrospective review.

Introduction: Metastatic uveal melanoma (mUM) is a difficult to treat disease. The liver is the primary site of metastasis in most patients, though uveal melanoma spreads widely in advanced disease. The only FDA approved immunotherapy medication for metastatic uveal melanoma is the HLA-A02:01 restricted bispecific T cell engager drug, Tebentafusp. Checkpoint inhibitor strategies and combination approaches have been tried with some limited success. We describe our experience treating patients at the University of Minnesota. Methods: Patients were included if they had biopsy-confirmed mUM. Twenty-five (25) patients meeting the criteria were identified. Medical records were reviewed and data extracted for patient baseline characteristics and response to treatments. Results: Median time to metastasis from the time of local therapy to the eye was 14.2 months (IQR; 9.3-22.0), and first site of metastasis was liver in 92% of patients. Two patients (8%) did not receive systemic therapy or radiation therapy for metastatic disease. Twenty-three (92%) patients received systemic therapy, 13 patients (52%) received ipilimumab-nivolumab as the first-line, while 4 patients (16%) received pembrolizumab. Landmark survival analysis by receipt of systemic therapy and radiation therapy treatments within 6 months of biopsy confirmed diagnosis is shown. Twenty patients (80%) received systemic therapy within 6 months of mUM diagnosis. Thirteen patients (52%) received liver directed radiation therapy within 6 months of mUM diagnosis. Discussion: Within our cohort, there was no overall survival benefit for patients receiving treatment of metastatic disease within 6 months of mUM diagnosis, versus those electing later or no treatment at all. There was remarkable clinical activity of ipilimumab and nivolumab in a subset of patients with mUM, in agreement with prior studies, and metastatic PD-L1 positive tumors were associated with a prolonged survival.

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone.

Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. Design: Randomized, masked multicenter study. Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy (P < 0.001, P < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality (P < 0.001) and empathy (P < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response (P = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content (P = 0.35), missing content (P = 0.001), extent of possible harm (P = 0.356), and likelihood of possible harm (P = 0.129). Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article.

Trends in the Clinical Presentation of Uveal Melanoma During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: The objective was to evaluate factors associated with clinical presentation of uveal melanoma (UM) during the initial two years of the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: This was a multi-site, retrospective cohort study of patients treated for uveal melanoma during the first (early) and second (late) year of the pandemic compared with the year prior (control). RESULTS: A total of 48, 67, and 75 patients were in the control, early, and late cohorts, respectively. The early cohort had a higher frequency of large tumors (control: 29.2%, early: 40.3%, late: 29.3%; P < 0.001) at presentation. Both the early and late cohorts had higher rates of enucleation (control: 8.33%, early: 20.9%, late: 18.67%; P ≤ 0.0338) compared to the control cohort. CONCLUSIONS: While there was an increase in large tumors along with a rise in enucleation during the first year of the pandemic, enucleation rates remained elevated even while tumor sizes normalized. [Ophthalmic Surg Lasers Imaging Retina 2024;55:278-284.].

PROPHYLACTIC TREATMENT OF LATTICE DEGENERATION IN FELLOW EYES AFTER REPAIR OF UNCOMPLICATED PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate prophylactic treatment (PTx) of lattice degeneration (LD) on retinal tear (RT) and rhegmatogenous retinal detachment (RRD) risk in fellow eyes of patients after primary RRD repair in the first eye. METHODS: This was a consecutive case series with cohort control involving patients with RRD repair from January 1, 2013, through December 31, 2017. Patients received PTx (PTx cohort) or no PTx (No-PTx cohort) in fellow eye with 5-year follow-up. Primary outcome measure was proportion with new fellow eye RT/RRD. Secondary outcomes included logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and status of myopia, posterior vitreous detachment, and pseudophakia. RESULTS: Four hundred ninety-eight patients were divided into 146 and 352 in PTx and No-PTx cohorts, respectively. PTx cohort developed significantly ( P < 0.05) fewer RT/RRD (17%) than No-PTx cohort (41%). PTx significantly ( P < 0.05) lowered RT/RRD irrespective of posterior vitreous detachment and myopia status. PTx patients undergoing phacoemulsification demonstrated significantly ( P < 0.05) less RT/RRD (22%) than No-PTx cohort (31%). There was no significant ( P = 0.96) final BCVA difference between PTx (median = 0 logMAR) and No-PTx (median = 0 logMAR) cohorts. CONCLUSION: PTx of asymptomatic fellow eye LD reduced RT/RRD risk.

BILATERAL EYE PATCHING MAY IMPROVE CLINICAL OUTCOMES FOR ACUTE PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: Evaluate preoperative bilateral eye patching (BEP) on subretinal fluid and vision in acute primary rhegmatogenous retinal detachments (RRDs). METHODS: Retrospective nonrandomized interventional study of 335 patients with RRD undergoing BEP until surgery (BEP cohort) and separated by the percentage of full-time compliance: high (≥90%), medium (>90% but ≥50%), and low (<50%). Those declining BEP were included (control). All underwent surgery and were followed for ≥3 months. Imaging was obtained immediately before surgery. Best-corrected visual acuity was measured at the longest follow-up and immediately before surgery. SRF and foveal status immediately before surgery were analyzed. RESULTS: Two hundred and forty and 95 patients were in BEP and control cohorts, respectively. Thirty patients presented immediately before surgery for analysis. High (64%) and medium (35%) compliance showed significantly greater ( P < 0.01) SRF reduction compared with low (4%) and control (3%). Mac-off RRD showed significantly greater ( P < 0.01) foveal reattachment with high (29%) and medium (8%) compliance compared with low (2%) and control (1%). Mac-on RRD demonstrated no significant differences ( P ≥ 0.51) in final best-corrected visual acuity among high (0 logarithm of the minimum angle of resolution [logMAR] [median], 20/20 Snellen), medium (0.10 logMAR, 20/25 Snellen), low (0.10 logMAR), and control cohorts (0.10 logMAR). Mac-off RRD demonstrated significantly better final best-corrected visual acuity with high compliance (0.30 logMAR, 20/40 Snellen) compared with low (0.40 logMAR, 20/50 Snellen; P = 0.04) and control (0.60 logMAR, 20/80 Snellen; P = 0.02). CONCLUSION: Preoperative BEP can stabilize or improve subretinal fluid in acute primary RRD. Patients with BEP >50% of the time experienced the greatest benefits.

CHOROIDAL NEVUS ASSOCIATED WITH VITELLIFORM DEPOSITION IN A PATIENT WITH AUTOSOMAL DOMINANT BEST DYSTROPHY.

BACKGROUND/PURPOSE: To describe the clinical, optical coherence tomography (OCT), fundus autofluorescence and ultrasound findings of a patient with a choroidal nevus actively exuding vitelliform material in the setting of autosomal dominant Best dystrophy (BD). METHODS: The patient's clinical course was followed over time with ophthalmic examinations and multimodal imaging. RESULTS: A 71-year-old male patient with BD was referred for evaluation of a choroidal nevus in the right eye. Dilated fundoscopic examination showed a small pigmented choroidal nevus in the temporal periphery. Over a 3-year period, the nevus developed progressive deposition of vitelliform material along its inferior border. Meanwhile, OCT and fundus photography showed only slight growth. Ultrasound showed no change in height; basal measurements were confounded by the increased vitelliform deposits. Genetic testing confirmed a heterozygous mutation in the BEST1 gene and electrophysiology was consistent with BD. CONCLUSIONS: Dysfunction of the retinal pigment epithelium associated with BD may cause novel presentations of other conditions such as choroidal nevi. The implication for malignant transformation of a choroidal nevus associated with vitelliform deposit accumulation in this context is unknown.

Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo.

Single-cell analysis in living humans is essential for understanding disease mechanisms, but it is impractical in non-regenerative organs, such as the eye and brain, because tissue biopsies would cause serious damage. We resolve this problem by integrating proteomics of liquid biopsies with single-cell transcriptomics from all known ocular cell types to trace the cellular origin of 5,953 proteins detected in the aqueous humor. We identified hundreds of cell-specific protein markers, including for individual retinal cell types. Surprisingly, our results reveal that retinal degeneration occurs in Parkinson's disease, and the cells driving diabetic retinopathy switch with disease stage. Finally, we developed artificial intelligence (AI) models to assess individual cellular aging and found that many eye diseases not associated with chronological age undergo accelerated molecular aging of disease-specific cell types. Our approach, which can be applied to other organ systems, has the potential to transform molecular diagnostics and prognostics while uncovering new cellular disease and aging mechanisms.

Biobanking of Human Aqueous and Vitreous Liquid Biopsies for Molecular Analyses.

A critical challenge in translational research is establishing a viable and efficient interface between patient care in the operating room (OR) and the research laboratory. Here, we developed a protocol for acquiring high-quality liquid biopsies for molecular analyses from the aqueous humor and the vitreous from patients undergoing eye surgery. In this workflow, a Mobile Operating Room Lab Interface (MORLI) cart equipped with a computer, a barcode scanner, and lab instruments, including onboard cold storage, is used to obtain and archive human biological samples. A web-based data privacy-compliant database enables annotating each sample over its lifetime, and a cartesian coordinate system allows tracking each barcoded specimen in storage, enabling quick and accurate retrieval of samples for downstream analyses. Molecular characterization of human tissue samples not only serves as a diagnostic tool (e.g., to distinguish between infectious endophthalmitis and other non-infectious intraocular inflammation) but also represents an important component of translational research, allowing the identification of new drug targets, development of new diagnostic tools, and personalized therapeutics.

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.

Spontaneous Improvement of Myopic Retinoschisis Following a Long-term Observational Period: A Case Series.

PURPOSE: To highlight spontaneous resolution or improvement of myopic retinoschisis (MR) in actively surveilled patients. METHODS: Case series of five patients diagnosed with MR who did not undergo pars-plana vitrectomy and were carefully monitored by a single retina specialist. Ocular and medical history were reviewed, and clinical characteristics including visual acuity, and the status of the MR were monitored with spectral domain ocular coherence tomography (SD-OCT) at each clinic visit. RESULTS: Five patients with were identified to have MR without vitreomacular traction, or macular hole formation. Two patients exhibited spontaneous and complete resolution of MR without surgical intervention over an average observation time of 52.5 months. In these cases, a clinical posterior vitreous detachment (PVD) was documented preceding the resolution of MR over an average time of 26.5 months. Snellen best corrected visual acuity (BCVA) in these patients were improved (Case 1 from 20/50 to 20/40, Case 2 from 20/30 to 20/25). The remaining three patients were monitored for an average of 52 months and showed improvement of MR via OCT imaging. Snellen BCVA either remained stable or improved from baseline (Case 3 stable at 20/30, Case 4 improved from 20/40 to 20/30, and Case 5 stable at 20/20). CONCLUSION: These findings suggest that conservative management of MR with observation can be considered especially in patients with challenging co-morbidities (such as monocular status), and with a clinically identified posterior vitreous detachment without vitreomacular traction.

Clinical Factors and Outcomes of Acute-Onset Endophthalmitis Following Small-Gauge Pars Plana Vitrectomy Surgery.

BACKGROUND AND OBJECTIVES: Describe risk factors, findings, and outcomes of acute endophthalmitis (AE) following small-gauge pars plana vitrectomy (PPV). PATIENTS AND METHODS: This was a retrospective single-center, nonrandomized study of post-PPV AE patients from 2013 to 2021. All received vitreous biopsy before treatment. Patients were divided into cohorts: 1) PPV within 3 days of diagnosis (Urgent-PPV), and 2) no urgent PPV (Other-treatment [Tx]). Main outcome was best-corrected visual acuity (BCVA) at 6 months. RESULTS: Twenty-one patients were analyzed. Epiretinal membrane was the most common indication for PPV (48%). Incidence was 0.074%. Culture-positive rate was 57%. For final BCVA, there was no significant (P = 0.85) difference between Urgent-PPV (median = 0.40 logMAR) and Other Tx cohorts (median = 0.35 logMAR). Sclerotomy wounds were not sutured in 71% of patients. Approximately 24% and 38% of patients analyzed had either no tamponade or partial tamponade, respectively. CONCLUSION: Tamponade agents and sclerotomy suturing may be important factors when evaluating post-small-gauge PPV-associated AE. Further studies are necessary for clarification. [Ophthalmic Surg Lasers Imaging Retina 2023;54:395-400.].

Evaluation of Outcomes of Acute Cataract Surgery-Related Endophthalmitis Using a Novel Management Algorithm Based on Presenting Risk Factors.

PURPOSE: Develop treatment algorithm for acute endophthalmitis (AE) following cataract surgery. METHODS: Retrospective single-center, non-randomized interventional study involving patients with AE divided into cohorts according to our novel scoring system, the Acute Cataract surgery-related Endophthalmitis Severity (ACES) score. Total score ≥3 points indicated need for urgent pars plana vitrectomy (PPV; within 24 hours), whereas <3 points indicated urgent PPV was unnecessary. Patients were retrospectively evaluated for visual outcomes based on whether their clinical course followed with or deviated from ACES score recommendations. Main outcome was best-corrected visual acuity (BCVA) at 6-month or longer after treatment. RESULTS: Total of 150 patients were analyzed. Patients whose clinical course followed the ACES score recommendation for immediate surgery had significantly (P < 0.01) better final BCVA (median = 0.18 logMAR, 20/30 Snellen) compared to those that deviated (median = 0.70 logMAR, 20/100 Snellen). For those where the ACES score deemed urgent PPV was unnecessary, no significant (P = 0.19) difference was observed between patients that followed with (median = 0.18 logMAR, 20/30 Snellen) and those that deviated from (median = 0.10 logMAR, 20/25 Snellen) recommendation. CONCLUSIONS: The ACES score may potentially provide critical and updated management guidance at presentation for when to recommend urgent PPV for patients suffering from post-cataract surgery AE.

Evolving Trends for the Clinical Presentation of Primary Rhegmatogenous Retinal Detachments From Early to Late Phases of the COVID-19 Pandemic.

OBJECTIVE: To evaluate the impact on trends in clinical presentation of acute, primary rhegmatogenous retinal detachments (RRD) from early to late phases of the COVID-19 pandemic. METHODS: This study was a single-center, consecutive case series of 1,727 patients treated after vaccine availability ("late"; 3/29/21 to 9/26/21), corresponding time frame in previous year of pandemic ("early"; 3/30/20 to 9/27/20), and prior to pandemic ("pre"; 4/1/19 to 9/29/19). Primary outcome was proportion of patients presenting with macula-off RRD. Secondary outcomes included best-corrected visual acuity (BCVA) and primary proliferative vitreoretinopathy (PVR). RESULTS: While macula-off RRD rates were significantly (P < 0.0001) elevated in early and late cohorts compared to the pre cohort, only the early cohort showed a significant (P < 0.0001) increase in both primary PVR presentation and complex RRD repair. Patients lost to follow-up in early cohort were significantly (P < 0.0001) higher than others. Early cohort showed significantly (P < 0.0001) worse final BCVA compared to others. CONCLUSION: Patients in late pandemic were less likely to exhibit clinical features of worse RRD disease and have improved visual outcomes compared to those in early pandemic. [Ophthalmic Surg Lasers Imaging Retina 2023;54:78-83.].

CLINICAL OUTCOMES OF ACUTE ENDOPHTHALMITIS AFTER INTRAVITREAL DELIVERY OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS VERSUS STEROIDS.

PURPOSE: To compare patients with acute endophthalmitis after intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors vs. steroids. METHODS: Retrospective single-center, nonrandomized interventional study from 2013 to 2021.Patients underwent vitreous biopsy before initiating treatment and were divided into the following cohorts: (1) anti-VEGF managed medically (T&I-anti-VEGF), (2) anti-VEGF managed by immediate pars plana vitrectomy (PPV-anti-VEGF), and (3) steroid therapy and managed medically or by pars plana vitrectomy (steroid). RESULTS: A total of 141 patients were analyzed. The steroid cohort demonstrated significantly worse presenting (median = 2.80 logarithm of the minimum angle of resolution [logMAR]; P ≤ 0.01) and final (median = 2.30 logMAR) best-corrected visual acuity compared with T&I-anti-VEGF (presenting: median = 2.00 logMAR; final: median = 0.40 logMAR) and pars plana vitrectomy-anti-VEGF cohorts (presenting: median = 2.30 logMAR; final: median = 0.48 logMAR). There was no significant ( P = 0.33) difference in the final best-corrected visual acuity between T&I-anti-VEGF and pars plana vitrectomy-anti-VEGF cohorts. There were no significant ( P ≥ 0.63) differences among cohorts in best-corrected visual acuity before acute endophthalmitis diagnosis (T&I-anti-VEGF: median = 0.40 logMAR; pars plana vitrectomy-anti-VEGF: median = 0.40 logMAR; steroid: median = 0.44 logMAR). Microbial cultures revealed similar profiles for all cohorts. CONCLUSION: Acute endophthalmitis after intravitreal injection steroid therapy had worse outcomes compared with anti-VEGF therapy.

Intraoperative Complications With Vitreous Biopsy for Molecular Proteomics.

OBJECTIVE: To study the incidence of intraoperative complications while collecting a vitreous sample for proteomic biomarker analyses during small-gauge pars plana vitrectomy (PPV). METHODS: A retrospective case series was assembled from the surgical logs and charts of patients who underwent 23-, 25-, and 27-gauge PPV along with an undiluted vitreous biopsy. Primary surgical indication and detailed operative reports were reviewed. Complications specific to vitreous biopsy were assessed while complications related to vitrectomy in general without biopsy were not tabulated. RESULTS: In 1190 eyes that underwent vitreous biopsy, the most common indications for PPV were rhegmatogenous retinal detachment (24.2%), epiretinal membrane (ERM) (21.7%), vitreous hemorrhage (11.0%), uveitis (8.3%), and macular hole (7.5%). An adequate sample of 0.5 cc to 1.0 cc was obtained in all cases. There was one sclerotomy break associated with biopsy, but no instances of lens touch, retinal contusion, retinal detachment, or intraocular hemorrhage. CONCLUSIONS: Undiluted vitreous biopsy obtained at the time of small-gauge vitrectomy is a generally safe procedure and may be considered for collection of samples for proteomic analysis. [Ophthalmic Surg Lasers Imaging Retina 2023;54:32-36.].

Sudden-onset unilateral painless vision loss.

A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.

INTRACTABLE PAIN AND DIPLOPIA AFTER SCLERAL BUCKLE SURGERY.

PURPOSE: To report a case of early postoperative scleral buckle slippage because of the dehiscence of scleral belt loop tunnels. METHOD: Case report. RESULTS: A 54-year-old woman presented with painful diplopia after a combination pars plana vitrectomy and scleral buckling procedure. Ocular movements were limited. Forced duction testing was restricted in all directions. Anterior slippage of the silicone band was suggested on computed tomography (CT) scans and was confirmed with surgical exploration. During surgery, it was found that thin-roofed scleral belt loop tunnels were dehisced in three quadrants leading to anterior slippage of the buckle. The displaced buckle was removed. Diplopia and pain resolved, and ocular motility improved immediately afterward. The retina remained attached at six months follow-up. A supplemental video summarizes the surgical findings and postoperative results. CONCLUSION: Spontaneous dehiscence of scleral belt loops may occur in thinly dissected scleral tunnels. Painful eye movement, diplopia, and a positive forced duction test should raise suspicion about a displaced scleral buckle. A CT scan may help with the diagnosis. Early diagnosis and immediate surgical intervention are needed to minimize patient discomfort and to improve long-term ocular motility.

COVID-19 Vaccination Hesitancy and Its Association With Altered Presentation of Primary Rhegmatogenous Retinal Detachment.

PURPOSE: Evaluate factors associated with coronavirus 2019 (COVID-19) vaccine hesitancy and clinical trends in primary rhegmatogenous retinal detachments (RRDs) during the first year of vaccine availability. DESIGN: Single-center, clinical cohort study. METHODS: Consecutive patients from December 14, 2020, to December 12, 2021, presenting vaccinated (Prior-), subsequently vaccinated (Later-), or remaining unvaccinated (Never-Vax). Primary outcome was proportion with macula-off (mac-off) RRD. Secondary outcomes included logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), primary proliferative vitreoretinopathy (PVR), proportion lost to follow-up, and distance traveled. RESULTS: 1047 patients were divided into 391 Prior-, 252 Later-, and 404 Never-Vax cohorts. Significantly greater proportions of Later- and Never-Vax cohorts presented with mac-off RRDs (Prior-Vax = 44.5%; Later-Vax = 54%, P < .0001; Never-Vax = 57.9%, P < .0001) and primary PVR (Prior-Vax = 4.3%; Later-Vax = 13.6%, P < .0001; Never-Vax = 17.1%, P < .0001) compared to Prior-Vax cohort. Significantly greater proportion of Never-Vax cohort (7.7%, P < .0001) were lost to follow-up compared to Prior- (2.3%) and Later-Vax (2.2%) cohorts. Never-Vax cohort (median = 35 miles) traveled farther compared to Prior- (median = 22.3 miles; P < .0001) and Later-Vax cohorts (25.45 miles; P = .0038). Prior-Vax cohort had significantly better (P < .05) initial (median = 0.30 logMAR) and final (0.18 logMAR) BCVA compared to Later- (Initial: 0.54 logMAR; Final: 0.30 logMAR) and Never-Vax (Initial: 0.70 logMAR; Final: 0.40 logMAR) cohorts. CONCLUSIONS: COVID-19 vaccine hesitancy is associated with worse clinical presentation and outcomes for primary RRD.

Multiple Genetically Distinct Uveal Melanomas Arise in the Same Eye of Two Patients with Melanosis Oculi.

PURPOSE: To determine whether unilateral multifocal uveal melanomas (UM) in the setting of ocular melanosis (melanosis oculi) represent genetically independent tumors. DESIGN: Clinical case series. METHODS: Two patients with unilateral multifocal UM in the setting of melanosis oculi were included. Tumors were evaluated for gene expression profile (GEP) and next generation sequencing (NGS) for uveal melanoma-associated mutations. Histopathologic analysis of enucleated specimens was also performed when available. RESULTS: Patients were both female, ages 73 and 83 years. In Patient #1, the tumors both exhibited Class 2 GEP but each harbored a unique BAP1 mutation. In Patient #2, one tumor was Class 1 and harbored an SF3B1 mutation, whereas the other tumor was Class 2 and harbored a BAP1 mutation. CONCLUSIONS: Unilateral multifocal UM in the setting of melanosis oculi can arise due to the development of genetically independent primary tumors, which is detectable based on the mutation profile of each tumor. This is the first report of genetically-confirmed independent primary tumors in the setting of unilateral multifocal UM.