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.

Noncanonical autophagy promotes the visual cycle.

Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components, but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents.

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.

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.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

STEM CELL THERAPIES, GENE-BASED THERAPIES, OPTOGENETICS, AND RETINAL PROSTHETICS: Current State and Implications for the Future.

PURPOSE: To review and discuss current innovations and future implications of promising biotechnology and biomedical offerings in the field of retina. We focus on therapies that have already emerged as clinical offerings or are poised to do so. METHODS: Literature review and commentary focusing on stem cell therapies, gene-based therapies, optogenetic therapies, and retinal prosthetic devices. RESULTS: The technologies discussed herein are some of the more recent promising biotechnology and biomedical developments within the field of retina. Retinal prosthetic devices and gene-based therapies both have an FDA-approved product for ophthalmology, and many other offerings (including optogenetics) are in the pipeline. Stem cell therapies offer personalized medicine through novel regenerative mechanisms but entail complex ethical and reimbursement challenges. CONCLUSION: Stem cell therapies, gene-based therapies, optogenetics, and retinal prosthetic devices represent a new era of biotechnological and biomedical progress. These bring new ethical, regulatory, care delivery, and reimbursement challenges. By addressing these issues proactively, we may accelerate delivery of care to patients in a safe, efficient, and value-based manner.

A subpopulation of activated retinal macrophages selectively migrated to regions of cone photoreceptor stress, but had limited effect on cone death in a mouse model for type 2 Leber congenital amaurosis.

BACKGROUND: Studies of antigen presentation in retina using mice that expressed green fluorescent protein (GFP) from a transgenic CD11c promoter found that retinal GFPhi cells possessed antigen presentation function. Subsequent studies found that these high GFPhi cells preferentially localized to sites of retinal injury, consistent with their APC function. Interest in the roles of macrophages in degenerative CNS diseases led us to study the GFPhi cells in a retinal model of neurodegeneration. We asked if apoptotic cone photoreceptor cell death in Rpe65-/- knockout mice induced the GFPhi cells, explored their relationship to resident microglia (MG), and tested their role in cone survival. METHODS: Rpe65-/- mice were bred to CD11cGFP mice on the B6/J background. CD11cGFPRpe65-/- mice were also backcrossed to CX3CR1YFP-creERROSADTA mice so that CX3CR1+ mononuclear cells could be depleted by Tamoxifen. Retinas were analyzed by immunohistochemistry, confocal microscopy, fluorescence fundoscopy and flow cytometry. RESULTS: Elevated numbers of GFPhi cells were concentrated in photoreceptor cell layers of CD11cGFPRpe65-/- mice coinciding with the peak of cone death at 2 to 4weeks of age, and persisted for at least 14months. After the initial wave of cone loss, a slow progressive loss of cones was found that continued to retain GFPhi cells in the outer retina. Sustained, four-week Tamoxifen depletions of the GFPhi cells and MG in Rpe65-/- mice from day 13 to day 41, and from day 390 to day 420 promoted a small increase in cone survival. We found no evidence that the GFPhi cells were recruited from the circulation; all data pointed to a MG origin. MG and GFPhi cells were well segregated in the dystrophic retina; GFPhi cells were foremost in the photoreceptor cell layer, while MG were concentrated in the inner retina. CONCLUSIONS: The expression of GFP on a subset of retinal mononuclear cells in CD11cGFP mice identified a distinct population of cells performing functions previously attributed to MG. Although GFPhi cells dominated the macrophage response to cone death in the photoreceptor cell layer, their ablation led to only an incremental increase in cone survival. The ability to identify, ablate, and isolate these cells will facilitate analysis of this activated, antigen-presenting subset of MG.

Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes.

A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease.

Retinol dehydrogenase 8 and ATP-binding cassette transporter 4 modulate dark adaptation of M-cones in mammalian retina.

KEY POINTS: This study explores the molecular mechanisms that regulate the recycling of chromophore required for pigment regeneration in mammalian cones. We report that two chromophore binding proteins, retinol dehydrogenase 8 (RDH8) and photoreceptor-specific ATP-binding cassette transporter (ABCA4) accelerate the dark adaptation of cones, first, directly, by facilitating the processing of chromophore in cones, and second, indirectly, by accelerating the turnover of chromophore in rods, which is then recycled and delivered to both rods and cones. Preventing competition with the rods by knocking out rhodopsin accelerated cone dark adaptation, demonstrating the interplay between rod and cone pigment regeneration driven by the retinal pigment epithelium (RPE). This novel interdependence of rod and cone pigment regeneration should be considered when developing therapies targeting the recycling of chromophore for rods, and evaluating residual cone function should be a critical test for such regimens targeting the RPE. ABSTRACT: Rapid recycling of visual chromophore and regeneration of the visual pigment are critical for the continuous function of mammalian cone photoreceptors in daylight vision. However, the molecular mechanisms modulating the supply of visual chromophore to cones have remained unclear. Here we explored the roles of two chromophore-binding proteins, retinol dehydrogenase 8 (RDH8) and photoreceptor-specific ATP-binding cassette transporter 4 (ABCA4), in dark adaptation of mammalian cones. We report that young adult RDH8/ABCA4-deficient mice have normal M-cone morphology but reduced visual acuity and photoresponse amplitudes. Notably, the deletion of RDH8 and ABCA4 suppressed the dark adaptation of M-cones driven by both the intraretinal visual cycle and the retinal pigmented epithelium (RPE) visual cycle. This delay can be caused by two separate mechanisms: direct involvement of RDH8 and ABCA4 in cone chromophore processing, and an indirect effect from the delayed recycling of chromophore by the RPE due to its slow release from RDH8/ABCA4-deficient rods. Intriguingly, our data suggest that RDH8 could also contribute to the oxidation of cis-retinoids in cones, a key reaction of the retina visual cycle. Finally, we dissected the roles of rod photoreceptors and RPE for dark adaptation of M-cones. We found that rods suppress, whereas RPE promotes, cone dark adaptation. Thus, therapeutic approaches targeting the RPE visual cycle could have adverse effects on the function of cones, making the evaluation of residual cone function a critical test for regimens targeting the RPE.

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.

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.

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.].

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.

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.

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.].

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.

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.].