Contrast Sensitivity Better Reflects Wide-Field Swept-Source Optical Coherence Tomography Angiography Vascular Metrics Among Healthy Eyes Compared to Visual Acuity.

BACKGROUND AND OBJECTIVE: To evaluate the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) and visual function in healthy eyes. PATIENTS AND METHODS: Fifty-seven eyes of 45 patients were evaluated with visual acuity (VA), contrast sensitivity (CS), and WF SS-OCTA (3 × 3, 6 × 6, and 12 × 12 mm images) on the same day. Mixed-effects multivariable regression analyses were performed. RESULTS: Contrast sensitivity metrics, including CS between 6 to 18 cycles per degree (cpd) and area under the logarithm CS function, were significantly associated with vessel density (VD) and vessel skeletonized density (VSD), whereas VA was not. The largest effect size was between CS at 18 cpd and VD (ß = 0.41, P = 0.007) and VSD (ß = 0.42, P = 0.006) on 12 × 12 mm images. CONCLUSIONS: Reduced VSD and VD on WF SSOCTA was significantly associated with decreased CS, whereas VA was not. These results suggest CS could serve as a screening tool for early stage retinal and neurologic disorders. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Structure-based network analysis predicts pathogenic variants in human proteins associated with inherited retinal disease.

Advances in gene sequencing technologies have accelerated the identification of genetic variants, but better tools are needed to understand which are causal of disease. This would be particularly useful in fields where gene therapy is a potential therapeutic modality for a disease-causing variant such as inherited retinal disease (IRD). Here, we apply structure-based network analysis (SBNA), which has been successfully utilized to identify variant-constrained amino acid residues in viral proteins, to identify residues that may cause IRD if subject to missense mutation. SBNA is based entirely on structural first principles and is not fit to specific outcome data, which makes it distinct from other contemporary missense prediction tools. In 4 well-studied human disease-associated proteins (BRCA1, HRAS, PTEN, and ERK2) with high-quality structural data, we find that SBNA scores correlate strongly with deep mutagenesis data. When applied to 47 IRD genes with available high-quality crystal structure data, SBNA scores reliably identified disease-causing variants according to phenotype definitions from the ClinVar database. Finally, we applied this approach to 63 patients at Massachusetts Eye and Ear (MEE) with IRD but for whom no genetic cause had been identified. Untrained models built using SBNA scores and BLOSUM62 scores for IRD-associated genes successfully predicted the pathogenicity of novel variants (AUC = 0.851), allowing us to identify likely causative disease variants in 40 IRD patients. Model performance was further augmented by incorporating orthogonal data from EVE scores (AUC = 0.927), which are based on evolutionary multiple sequence alignments. In conclusion, SBNA can used to successfully identify variants as causal of disease in human proteins and may help predict variants causative of IRD in an unbiased fashion.

Widefield, Swept-Source Optical Coherence Tomography Angiography Metrics as Predictors of Anti-VEGF Treatment in Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: Our objective was to assess baseline widefield swept-source optical coherence tomography angiography (WF SSOCTA) microvascular metrics as predictors for the number of anti-vascular endothelial growth factor (VEGF) injections and visual acuity (VA) at 12-months follow-up in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: This was a prospective study including 49 RVO eyes from 49 patients who had not received an anti-VEGF injection for at least 3 months prior to imaging. Microvascular metrics from 6×6-mm and 12×12-mm angiograms were assessed using linear regression models, adjusting for age. RESULTS: Reductions in the vessel density (VD) and vessel skeletonized density (VSD) vascular metrics were associated both with a higher number of anti-VEGF injections at all follow-up time points and reduced VA 12 months after imaging in all RVO eyes. CONCLUSIONS: WF SS-OCTA VD and VSD micro-vascular metrics at baseline can prognosticate VA and number of anti-VEGF injections required at 3, 6, and 12 months in RVO eyes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

Early recurrence of macular schisis in X-linked retinoschisis treated with vitrectomy for rhegmatogenous retinal detachment under silicone oil: case report and brief literature review.

X-linked retinoschisis (XLRS) is an inherited retinal degeneration affecting males, characterized by splitting of the retinal layers. We herein present the outcomes of surgical treatment in a case of XLRS complicated by rhegmatogenous retinal detachment (RRD). A 22-year-old male presented to the emergency department due to decreased visual acuity and visual field defect in his left eye Oculus Sinister (OS) of 1 week duration. The patient reported an early onset retinal degeneration and decreased visual acuity in both eyes since childhood in his past ocular history. Upon presentation, best corrected visual acuity (BCVA) was 6/30 on the right eye Oculus Dexter (OD) and 6/120 OS. Fundus examination revealed areas of peripheral retinal schisis, and the characteristic spoke wheel pattern on the macula of both eyes. In OS, a temporal RRD involving the macula was identified. The patient underwent surgical treatment with pars plana vitrectomy with internal limiting membrane (ILM) peeling, endolaser, and silicone oil (SO) tamponade. BCVA in OS improved to 6/60 and schistic cavities resolution was observed in the immediate postoperative period. The patient's BCVA further improved to 6/19 at 1 month, as foveal anatomy showed relative improvement. However, there was a rapid reappearance of schisis spaces in the macular area at this point, which was also followed by progressive deterioration of foveal schisis by 3 months post-operatively. The resorption and recurrence of lamellar macular schisis changes after ILM peel and presence of SO, highlights that although XLRS findings can temporarily improve upon surgical intervention, the pathogenetic mechanisms contributing to disease phenotype remain to be elucidated.

Quantitative Contrast Sensitivity Function and the Effect of Aging in Healthy Adult Eyes: A Normative Database.

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:212-219.].

Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection.

PURPOSE: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing. DESIGN: Pilot study using ex vivo human eyes. METHODS: Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 µL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 µL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors. RESULTS: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 µL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx. CONCLUSIONS: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.

Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review.

Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.

Impact of phacoemulsification on posterior vitreous detachment formation in eyes with vitreomacular traction.

Purpose: To investigate the impact of phacoemulsification on posterior vitreous detachment formation in eyes with vitreomacular traction (VMT) with or without macular holes. Methods: A retrospective search of the medical records was conducted to identify patients with VMT who underwent cataract surgery at Mass Eye and Ear from 2016 to 2021. Patient demographics, ocular comorbidities, and clinical characteristics were extracted from the record, and optical coherence tomography images were assessed to confirm VMT and the presence of a lamellar or full-thickness macular hole (FMTH). Patients who underwent vitrectomy prior to cataract surgery were excluded. Results: A total of 22 patients (15 women [68%]) met inclusion criteria (average age, 71 years). Fifteen eyes had an associated epiretinal membrane (63%), 7 had a lamellar hole (29%), and 8 had an FTMH (33%). Epiretinal membrane was present in 3 of 7 eyes with lamellar holes (43%) and 4 of 8 with a FTMH (50%). No eyes developed a complete posterior vitreous detachment following phacoemulsification. In 2 cases, there was progression of the macular hole stage following phacoemulsification. Ten eyes underwent subsequent pars plana vitrectomy (PPV). There was no statistically significant difference in visual acuity between eyes pre- and post-phacoemulsification; however, there was a statistically significant improvement in visual acuity pre- and post-PPV. Conclusions: Unlike other studies, in this case series of 24 eyes with VMT or VMT with holes, no cases of full posterior vitreous detachment occurred following unremarkable phacoemulsification or YAG capsulotomy.

Opposing Roles of Blood-Borne Monocytes and Tissue-Resident Macrophages in Limbal Stem Cell Damage after Ocular Injury.

Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed this is mediated directly by the caustic agent. Here we show that LSC damage occurs through immune cell mediators, even without direct injury to LSCs. In particular, pH elevation in the anterior chamber (AC) causes acute uveal stress, the release of inflammatory cytokines at the basal limbal tissue, and subsequent LSC damage and death. Peripheral C-C chemokine receptor type 2 positive/CX3C motif chemokine receptor 1 negative (CCR2+ CX3CR1-) monocytes are the key mediators of LSC damage through the upregulation of tumor necrosis factor-alpha (TNF-α) at the limbus. In contrast to peripherally derived monocytes, CX3CR1+ CCR2- tissue-resident macrophages have a protective role, and their depletion prior to injury exacerbates LSC loss and increases LSC vulnerability to TNF-α-mediated apoptosis independently of CCR2+ cell infiltration into the tissue. Consistently, repopulation of the tissue by new resident macrophages not only restores the protective M2-like phenotype of macrophages but also suppresses LSC loss after exposure to inflammatory signals. These findings may have clinical implications in patients with LSC loss after chemical burns or due to other inflammatory conditions.

Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes.

PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD). METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA. RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study's follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p < 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p < 0.001), eye (p = 0.003), and time-eye interaction (p < 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (p = 0.015). CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.

The NLRP3 inflammasome - interleukin 1ß axis in uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1ß axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P < 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1ß secretion than CM, especially when compared to the Hs294t cell line (P < 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1ß compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1ß secretion by melanoma cells and highlight differences between CM and UM.

The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration.

PURPOSE: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN: Retrospective cohort study. PARTICIPANTS: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES: Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001). CONCLUSIONS: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

Referable Macular Hemorrhage-A Clinically Meaningful Screening Target in Newborn Infants. Position Statement of the Association of Pediatric Retina Surgeons.

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. "Referral warranted" eye disease is present at birth in about 5.5% of term infants, with "macular hemorrhage impinging on the fovea" representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on "referable macular hemorrhage" (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:3-6.].

Aflibercept for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of aflibercept in retinopathy of prematurity (ROP). PATIENTS AND METHODS: We performed a systematic review and meta-analysis of proportions from the literature in PubMed and Cochrane Library using search terms related to the use of aflibercept in ROP. Studies in non-preterm infants or that did not use aflibercept as the initial treatment were excluded. Risk of bias was assessed by the ROBINS-I (Risk Of Bias in Non-randomized Studies of Interventions) tool. RESULTS: We identified six case series. Collectively, 218 eyes were treated with aflibercept for ROP. We found an average 97% (95% confidence interval [CI], 93% to 99%) regression rate with aflibercept and an average 16% (95% CI, 5% to 41%) recurrence rate. With the exception of one outlier study, these numbers are similar to previous reports using anti-vascular endothelial growth factor (VEGF) agents in ROP. CONCLUSIONS: Aflibercept holds promise for use in ROP and has been demonstrated to be efficacious in six case series. Randomized, controlled clinical trials appear warranted to compare aflibercept with other anti-VEGF agents. [Ophthalmic Surg Lasers Imaging. 2021;52:673-681.].

Genomic-Metabolomic Associations Support the Role of LIPC and Glycerophospholipids in Age-Related Macular Degeneration.

PURPOSE: Large-scale genome-wide association studies (GWAS) have reported important single nucleotide polymorphisms (SNPs) with significant associations with age-related macular degeneration (AMD). However, their role in disease development remains elusive. This study aimed to assess SNP-metabolite associations (i.e., metabolite quantitative trait loci [met-QTL]) and to provide insights into the biological mechanisms of AMD risk SNPs. DESIGN: Cross-sectional multicenter study (Boston, Massachusetts, and Coimbra, Portugal). PARTICIPANTS: Patients with AMD (n = 388) and control participants (n = 98) without any vitreoretinal disease (> 50 years). METHODS: Age-related macular degeneration grading was performed using color fundus photographs according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and evaluated with mass spectrometry for metabolomic profiling and Illumina OmniExpress for SNPs profiling. Analyses of met-QTL of endogenous metabolites were conducted using linear regression models adjusted for age, gender, smoking, 10 metabolite principal components (PCs), and 10 SNP PCs. Additionally, we analyzed the cumulative effect of AMD risk SNPs on plasma metabolites by generating genetic risk scores and assessing their associations with metabolites using linear regression models, accounting for the same covariates. Modeling was performed first for each cohort, and then combined by meta-analysis. Multiple comparisons were accounted for using the false discovery rate (FDR). MAIN OUTCOME MEASURES: Plasma metabolite levels associated with AMD risk SNPs. RESULTS: After quality control, data for 544 plasma metabolites were included. Meta-analysis of data from all individuals (AMD patients and control participants) identified 28 significant met-QTL (ß = 0.016-0.083; FDR q-value < 1.14 × 10-2), which corresponded to 5 metabolites and 2 genes: ASPM and LIPC. Polymorphisms in the LIPC gene were associated with phosphatidylethanolamine metabolites, which are glycerophospholipids, and polymorphisms in the ASPM gene with branched-chain amino acids. Similar results were observed when considering only patients with AMD. Genetic risk score-metabolite associations further supported a global impact of AMD risk SNPs on the plasma metabolome. CONCLUSIONS: This study demonstrated that genomic-metabolomic associations can provide insights into the biological relevance of AMD risk SNPs. In particular, our results support that the LIPC gene and the glycerophospholipid metabolic pathway may play an important role in AMD, thus offering new potential therapeutic targets for this disease.

Targeting the YAP/TAZ Pathway in Uveal and Conjunctival Melanoma With Verteporfin.

Purpose: The purpose of this study was to determine whether YAP/TAZ activation in uveal melanoma (UM) and the susceptibility of melanoma cell lines to YAP/TAZ inhibition by verteporfin (VP) is related to the tumor's genetic background. Methods: Characteristics of 144 patients with enucleated UM were analyzed together with mRNA expression levels of YAP/TAZ-related genes (80 patients from the The Cancer Genome Atlas [TCGA] project and 64 patients from Leiden, The Netherlands). VP was administered to cell lines 92.1, OMM1, Mel270, XMP46, and MM28 (UM), CRMM1 and CRMM2 (conjunctival melanoma), and OCM3 (cutaneous melanoma). Viability, growth speed, and expression of YAP1-related proteins were assessed. Results: In TCGA data, high expression of YAP1 and WWTR1 correlated with the presence of monosomy 3 (P = 0.009 and P < 0.001, respectively) and BAP1-loss (P = 0.003 and P = 0.001, respectively) in the primary UM; metastasis development correlated with higher expression of YAP1 (P = 0.05) and WWTR1 (P = 0.003). In Leiden data, downstream transcription factor TEAD4 was increased in cases with M3/BAP1-loss (P = 0.002 and P = 0.006) and related to metastasis (P = 0.004). UM cell lines 92.1, OMM1, and Mel270 (GNAQ/11-mutation, BAP1-positive) and the fast-growing cell line OCM3 (BRAF-mutation) showed decreased proliferation after exposure to VP. Two slow-growing UM cell lines XMP46 and MM28 (GNAQ/11-mutation, BAP1-negative) were not sensitive to VP, and neither were the two conjunctival melanoma cell lines (BRAF/NRAS-mutation). Conclusions: High risk UM showed an increased expression of YAP/TAZ-related genes. Although most UM cell lines responded in vitro to VP, BAP1-negative and conjunctival melanoma cell lines did not. Not only the mutational background, but also cell growth rate is an important predictor of response to YAP/TAZ inhibition by VP.

Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration.

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography-mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

ALTITUDE-ASSOCIATED INTRAOCULAR PRESSURE CHANGES IN A GAS-FILLED EYE.

PURPOSE: Intraocular gases are commonly used in vitreoretinal surgery. Patients are routinely advised against air travel before the complete absorption of intraocular gas. Consequently, reports on air travel in patients with large intraocular gas bubbles are highly unusual. Here, we report the intraocular pressure changes of a patient ascending to an altitude of 2,600 feet in a helicopter with a 50% fill perfluoropropane (C3F8) gas bubble in his left eye. METHODS: Case report and literature review. RESULTS: A 61-year-old male patient underwent pars plana vitrectomy for a rhegmatogenous retinal detachment, with fluid-gas exchange using 16% C3F8. With a 50% fill bubble in the left eye, the patient took a short helicopter trip ascending to a maximum altitude of 2,600 feet. Before take-off, intraocular pressure in the operated eye was 14 mmHg. The average increase in intraocular pressure was 10.8 mmHg per 1,000 feet of ascent, with a maximum recorded intraocular pressure of 42 mmHg. The patient denied both ocular pain and loss of vision but did report changes in the appearance of the gas bubble meniscus at 2,100 feet. CONCLUSION: Short-term low-altitude air travel may be tolerated by some patients with intraocular gas in situ. Further studies are required to define the conditions by which patients with gas bubbles may fly safely.